Targeting the IPA and Matching for the Non-Inherited Maternal Antigen for Haplo-Cord Transplantation

Phase 2

Active, not recruiting

Conditions: Hematologic Malignancies

Interventions: Device: CliniMACS® CD34 Reagent System
Drug: Fludarabine
Drug: Melphalan
Drug: anti-thymocyte globulin (rabbit)
Drug: Rituximab
Radiation: Total Body Irradiation
Drug: Mycophenolate Mofetil
Drug: Tacrolimus

Registration Number: NCT01810588

Lead Sponsor: Weill Medical College of Cornell University

Brief Summary: In this trial, we aim to improve the outcomes of haplo cord transplant. Haplo cord transplant is a novel and promising way to improve transplant outcomes. We hypothesize that identification of a graft that is at least 5/6 matched and inherited paternal antigen (IPA) targeted (i.e., cord blood grafts share one or more IPA antigens with the prospective recipient) is more important to the outcome of haplo cord transplant than the nucleated cell dose. The identification of such a graft for a large proportion of the subjects may necessitate accepting a lower umbilical cord graft dose.

In addition to a umbilical cord blood transplant, recipients will receive stem cells from a family member ( a haplo-identical donor) . After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device. The subject will undergo a chemotherapy conditioning regimen prior to transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past.

Detailed Description: This is a clinical trial for subjects with hematologic malignancies ( acute leukemia, myeloproliferative disorders, lymphoma, myeloma) who are in need of a donor stem cell transplant, and for whom an umbilical cord blood transplant is thought to be the best option. As donors for allogeneic transplant, we typically try to use related family members, such as brothers or sisters, or volunteer donors who are 'HLA matched', i.e. share similar proteins on their cells. This study is for subjects for whom such a matched sibling donor or a matched unrelated donor is not available.

For such subjects a commonly used transplant procedure is to use stem cells from one or two umbilical cords (UCB) from a newborn. These umbilical cord blood grafts, despite not completely matching the recipient, cause few problems with graft vs host disease (a common complication of transplant). But they tend to grow very slowly and subjects often have very prolonged hospital stays and are at high risk for complications due to low blood counts. Umbilical cord blood transplant will be the standard arm for this protocol.

This study uses a new method of bone marrow transplantation called combined haplo-identical cord (haplo-cord) transplantation. In this procedure, cells from a related donor who shares half of the HLA proteins ( haplo-identical) are collected from the blood, as well as cells from an umbilical cord, and then both are transplanted. It is hoped that by using cells from a haplo-identical relative, subjects will have a faster recovery and require fewer transfusions. Over time the haplo-identical cells from the relative are replaced by the cells from the cord blood. The combined transplantation of haplo-identical stem cells and cord blood has previously been used in approximately 60 subjects with very encouraging results.

Traditionally it has been felt that the most important determinant of outcome of an UCB stem cell transplant is the cord blood cell dose. The second determinant is the degree of matching between donor and recipient. Many times, we have difficulty identifying UCB units of sufficient cell dose that are well matched. Of interest,in our prior study of haplo-cord SCT indicated outcomes seemed independent of the UCB cell dose. If this preliminary observation is correct, we may be able to improve the outcomes of haplo cord transplant further by accepting lower threshold UCB doses and rather focusing on optimal matching (including matching for HLA and another characteristic called IPA). This is the primary objective of this study.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 270

Inclusion Criteria

Subject must have a confirmed diagnosis of:
1. Previously Relapsed or refractory acute leukemia (myeloid or lymphoid)
2. Acute leukemia in first remission at high-risk for recurrence
3. Chronic myelogenous leukemia in chronic, accelerated phase or blast-crisis
4. Recurrent or refractory malignant lymphoma or Hodgkin lymphoma
5. Chronic lymphocytic leukemia, relapsed or with poor prognostic features
6. Multiple myeloma
7. Myelodysplastic syndrome
8. Chronic myeloproliferative disease
9. Hemoglobinopathies
10. Aplastic anemia
11. Other hematological disorder in need of allogeneic transplant (e.g. blastoid dendritic cell neoplasm)
Age ≥ 18 years
Likely to benefit from allogeneic transplant in the opinion of the transplant physician
An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.
Karnofsky (KPS) Performance status of >= 70%
Acceptable organ function as defined below: Serum bilirubin: < 2.0mg/dL ALT(SGPT): < 3 X upper limit of normal Creatinine Clearance: > 50 mL/min/1.73m2 (as estimated by the modified MDRD equation)
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Life expectancy is severely limited by concomitant illness or uncontrolled infection
Severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired pulmonary function tests (PFT's)
Evidence of chronic active hepatitis or cirrhosis
Uncontrolled HIV disease
Pregnant or lactating

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	CliniMACS® CD34 Reagent System	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	Total Body Irradiation	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	CliniMACS® CD34 Reagent System	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	Total Body Irradiation	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	CliniMACS® CD34 Reagent System	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	Total Body Irradiation	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	CliniMACS® CD34 Reagent System	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	Total Body Irradiation	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	Fludarabine	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	Melphalan	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	anti-thymocyte globulin (rabbit)	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	Rituximab	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	Mycophenolate Mofetil	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg	Tacrolimus	All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	Fludarabine	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	anti-thymocyte globulin (rabbit)	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	Melphalan	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	Rituximab	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	Mycophenolate Mofetil	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg	Tacrolimus	All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	Fludarabine	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	Melphalan	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	anti-thymocyte globulin (rabbit)	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	Rituximab	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	Mycophenolate Mofetil	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg	Tacrolimus	All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	Fludarabine	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	Rituximab	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	Melphalan	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	anti-thymocyte globulin (rabbit)	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	Mycophenolate Mofetil	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.
Cohort 4	Tacrolimus	All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, recipients will receive stem cells from a family member ( a haplo-identical donor). After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Who Achieved Engraftment With De-Escalating Umbilical Cord Total Nucleated Cell (TNC) Dose	100 days	We aim to identify the lowest threshold of umbilical cord total nucleated cell (TNC) dose that can be utilized assure durable umbilical cord blood engraftment in the haplo-cord transplants. The threshold will be defined as the lowest dose which assures cord blood engraftment occurs in at least 80% of subjects.

Secondary Outcome Measures

Name	Time	Method
Long-term Survival of Subjects Undergoing Haplo-cord Transplants	5 years after transplant	Evaluate the long term outcome of subjects undergoing haplo cord transplants using an optimally matched umbilical cord blood (UCB) graft (i.e. Survival, profession-free survival (PFS), Relapse, transplant-related mortality (TRM), toxicities, infections and GVHD)
Impact of IPA Targeting on Transplant Outcome	5 years from transplantation	As much as possible, UCB units will be chosen to be IPA targeted. This is not always possible. We will therefore also retrospectively analyze transplant outcomes and correlate with IPA status.
Impact of NIMA Matching on Transplant Outcome	5 years from transplantation	As much as possible, UCB units will be chosen to be NIMA matched. This is not always possible. We will therefore also retrospectively analyze transplant outcomes and correlate with NIMA status.

Trial Locations

Locations (2): Weill Cornell Medical College
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New York, New York, United States
University of Chicago Medical Center
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Chicago, Illinois, United States