Randomized HaploCord Blood Transplantation vs. Double Umbilical Cord Blood Transplantation for Hematologic Malignancies

Phase 2

Terminated

Conditions: Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Acute Lymphocytic Leukemia
Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma

Interventions: Device: CliniMACS® CD34 Reagent System
Drug: Fludarabine
Drug: Melphalan
Procedure: Double Umbilical Cord Blood Transplantation
Drug: Rabbit ATG
Procedure: Haplo-Identical Cord Transplantation

Registration Number: NCT01745913

Lead Sponsor: Weill Medical College of Cornell University

Brief Summary: The purpose of this study is compare the efficacy of haplo-cord transplant (investigational arm) with that of a more commonly used procedure in which only the cells contained in one or two umbilical cords are infused (standard arm).

We hypothesize that reduced intensity conditioning and haplo-cord transplant results in fast engraftment of neutrophils and platelets, low incidences of acute and chronic graft versus host disease, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay and promising long term outcomes. We also hypothesize that umbilical cord blood selection can prioritize matching and better matched donors can be identified rapidly for most subjects.

Detailed Description: This is a clinical trial for subjects with hematologic malignancies ( acute myelogenous leukemia, acute lymphocytic leukemia, Hodgkin's or Non-Hodgkin's lymphoma, or myelodysplastic syndrome) 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. For allogeneic transplant donors, 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.

This study tests 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.

The purpose of this study is to compare the efficacy of haplo-cord transplant ( "investigational" arm) with the more commonly used procedure in which only the cells contained in one or two umbilical cords are infused ("standard" arm). Subjects will be randomly assigned into either the haplo-cord group or the umbilical cord group.

If randomized to the haplo-cord group, a family member will undergo a stem cell collection. In both arms, subjects will receive a "conditioning regimen" prior to transplantation. The conditioning regimen consists of chemotherapy, which is meant to destroy the cancer cells and suppress the immune system to allow the transplanted cells to grow. Subjects will remain in the hospital until the stem cells are fully recovered, which is usually 4 to 6 weeks after the transplant. Subjects will have bone marrow aspiration and biopsy at 3 weeks, 4 weeks, 2 months, 6 months and 1 year after the transplant and then yearly thereafter. Participation in the study will continue for up to 5 years after transplantation.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

Inclusion Criteria

Subject must have a histologically or cytologically confirmed diagnosis of: Acute Myelogenous Leukemia Myelodysplastic Syndrome Acute Lymphocytic Leukemia Lymphoma (Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma)
Must be > 18 years of age
Subject is likely to benefit from allogeneic transplant in the opinion of the transplant physician
An human leukocyte antigen (HLA)-identical related or unrelated donor cannot be identified within an appropriate time frame
Karnofsky Performance Status (KPS) of > 80
Subject has acceptable organ and marrow function as defined below: Serum bilirubin < 2.0mg/dL ALT(SGPT) 3 X upper limit of normal Creatinine Clearance > 50 mL/min as estimated by the modified MDRD equation.18
Ability to understand and the willingness to sign a written informed consent document.
A preliminary search has identified both:
1. Appropriate umbilical cords for a single, or if necessary a double umbilical cord blood (UCB) transplant AND
2. An appropriate single UCB as well as an appropriate haplo donor for haplo-cord transplant

Exclusion Criteria

Myeloproliferative disorders, hemoglobinopathies, severe aplastic anemia or any diagnosis not listed under 3.1.1
Life expectancy is severely limited by concomitant illness or uncontrolled infection
Subjects with severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired pulmonary function tests (PFTs)
Subject has evidence of chronic active hepatitis or cirrhosis
Subject is HIV-positive
Subject is pregnant or lactating. -

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Haplo-Cord SCT	CliniMACS® CD34 Reagent System	The UCB unit must supply a minimum of 1.0 x107/kg pre-cryopreserved nucleated cell dose. The unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
Haplo-Cord SCT	Haplo-Identical Cord Transplantation	The UCB unit must supply a minimum of 1.0 x107/kg pre-cryopreserved nucleated cell dose. The unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
UCB SCT	Double Umbilical Cord Blood Transplantation	For the standard arm, UCB units will be selected using the Minnesota strategy and the strategy followed in a recent CTN study.17;19Each unit must supply a minimum of 1.5 x107/kg pre-cryopreserved nucleated cell dose. Subjects must have two partially HLA-matched UCB units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
Haplo-Cord SCT	Melphalan	The UCB unit must supply a minimum of 1.0 x107/kg pre-cryopreserved nucleated cell dose. The unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
Haplo-Cord SCT	Fludarabine	The UCB unit must supply a minimum of 1.0 x107/kg pre-cryopreserved nucleated cell dose. The unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
Haplo-Cord SCT	Rabbit ATG	The UCB unit must supply a minimum of 1.0 x107/kg pre-cryopreserved nucleated cell dose. The unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
UCB SCT	Fludarabine	For the standard arm, UCB units will be selected using the Minnesota strategy and the strategy followed in a recent CTN study.17;19Each unit must supply a minimum of 1.5 x107/kg pre-cryopreserved nucleated cell dose. Subjects must have two partially HLA-matched UCB units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
UCB SCT	Melphalan	For the standard arm, UCB units will be selected using the Minnesota strategy and the strategy followed in a recent CTN study.17;19Each unit must supply a minimum of 1.5 x107/kg pre-cryopreserved nucleated cell dose. Subjects must have two partially HLA-matched UCB units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1
UCB SCT	Rabbit ATG	For the standard arm, UCB units will be selected using the Minnesota strategy and the strategy followed in a recent CTN study.17;19Each unit must supply a minimum of 1.5 x107/kg pre-cryopreserved nucleated cell dose. Subjects must have two partially HLA-matched UCB units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1

Primary Outcome Measures

Name	Time	Method
Rate of Neutrophil Engraftment After Combined Haplo-identical Cord With That of Umbilical Cord Blood Transplantation.	estimation of 24 months to determine engraftment rates for all subjects	No patients completed this study and are therefore inevaluable. Subject data not evaluable for the outcome measure time frame. Subject data only evaluable up to month 3.

Secondary Outcome Measures

Name	Time	Method
Platelet Recovery After Transplant Regimens	estimation of 24 months to determine platelet recovery for all subjects	No patients completed this study and are therefore inevaluable
Transfusion Requirements After Haplo-identical Umbilical Cord Blood Transplant Versus Double Umbilical Cord Blood Transplant	estimation of 24 months to determine transfusion requirements of all subjects
Severity of Opportunistic Infections	estimation of 24 months to obtain infection data on all subjects
Transplant-related Mortality (TRM), Relapse Rate, Survival and Progression Free Survival	estimation of 24 months to obtain survival info between subjects
Incidence of Acute and Chronic GVHD	estimation of 24 months to obtain GVHD data on all subjects