HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide

Phase 2

Completed

• Conditions: Myelodysplastic Syndrome (MDS); Chronic Lymphocytic Leukemia (CLL); Chemotherapy-sensitive Lymphoma; Acute Lymphoblastic Leukemia (ALL)/T Lymphoblastic Lymphoma; Acute Myelogenous Leukemia (AML); Acute Biphenotypic Leukemia (ABL); Acute Undifferentiated Leukemia (AUL)
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5; Drug: Cyclophosphamide 50mg/kg/day IV on Days -5,-4; Radiation: Total Body Irradiation (TBI) 200cGy on Day -1; Drug: Cyclophosphamide 50mg/kg/day IV on Days -2,-1; Drug: Busulfan; Radiation: Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1; Procedure: Infusion of non-T-cell depleted bone marrow on Day 0; Drug: Post-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4; Drug: Sirolimus; Drug: Mycophenolate mofetil; Drug: G-CSF; Drug: Pre-HCT Mesna on Days -2 and -1; Drug: Pre-HCT Mesna on Days -5 and -4; Drug: Pre-HCT Mesna on Days -6 and -5; Drug: Post-HCT Mesna

• Registration Number: NCT02793544
• Lead Sponsor: Center for International Blood and Marrow Transplant Research

Brief Summary

This is a multi-center, single arm Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated bone marrow transplantation donors and post-transplantation cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil (MMF) for graft versus host disease (GVHD) prophylaxis in patients with hematologic malignancies.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-05-31
• Study First Submitted QC: 2016-06-02
• Study First Posted: 2016-06-08
• Study Start: 2016-12
• Primary Completion: 2020-03
• Study Completion: 2020-03
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-30
• Last Update Posted: 2020-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Age ≥ 15 years and < 71 years at the time of signing the informed consent form

2. Partially HLA-mismatched unrelated donor: HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, -C, and -DRB1 loci; a minimum match of 4/8 at HLA-A, -B, -C, and -DRB1 is required

3. Product planned for infusion is bone marrow

4. Disease and disease status:

   1. Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma; acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute undifferentiated leukemia (AUL)
   2. Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with de novo MDS who have or have previously had Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is not a requirement; Subjects must have < 20% bone marrow blasts, assessed within 60 days of informed consent; Subjects may have received prior therapy for the treatment of MDS prior to enrollment
   3. Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial response (PR) if FIC is to be used
   4. Chronic myeloid leukemia (CML) in 1st or subsequent chronic phase characterized by <10% blasts in the blood or bone marrow.
   5. Chemotherapy-sensitive lymphoma in status other than 1st CR

5. Performance status: Karnofsky or Lansky score ≥ 60% (Appendix A)

6. Adequate organ function defined as:

   1. Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 35% (RIC cohort) or LVEF at rest ≥ 40% (FIC cohort), or left ventricular shortening fraction (LVFS) ≥ 25%
   2. Pulmonary: diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume (FEV1), forced vital capacity (FVC) ≥ 50% predicted by pulmonary function tests (PFTs)
   3. Hepatic: total bilirubin ≤ 2.5 mg/dL, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) < 5 x upper limit of (ULN) (unless disease related)
   4. Renal: serum creatinine (SCr) within normal range for age (see table 2.3). If SCr is outside normal range for age, creatinine clearance (CrCl) > 40 mL/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault formula for those aged ≥ 18 years; by Original Schwartz estimate for those < 18 years))

7. Subjects ≥ 18 years of age must have the ability to give informed consent according to applicable regulatory and local institutional requirements. Legal guardian permission must be obtained for subjects < 18 years of age. Pediatric subjects will be included in age appropriate discussion in order to obtain assent.

8. Subjects with documentation of confirmed HIV-1 infection (i.e. HIV-positive), and a hematologic malignancy who meets all other eligibility requirements must:

   1. Receive only RIC regimen (i.e. Regimen A)
   2. Be willing to comply with effective antiretroviral therapy (ARV)
   3. Have achieved a sustained virologic response for 12 weeks after cessation of hepatitis C antiviral treatment (in HIV-positive subjects with hepatitis C)

Exclusion Criteria

1. HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor available. This exclusion does not apply to HIV-positive subjects who have a CCR5delta32 homozygous donor.

2. Autologous HCT < 3 months prior to the time of signing the informed consent form

3. Females who are breast-feeding or pregnant

4. HIV-positive subjects:

   1. Acquired immunodeficiency syndrome (AIDS) related syndromes or symptoms that may pose an excessive risk for transplantation-related morbidity as determined by the Treatment Review Committee (see Appendix D).
   2. Untreatable HIV infection due to multidrug ARV resistance. Subjects with a detectable or standard viral load > 750 copies/mL should be evaluated with an HIV drug resistance test (HIV-1 genotype). The results should be included as part of the ARV review (described in Appendix D).
   3. May not be currently prescribed ritonavir, cobacistat and/or zidovudine

5. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)

6. Prior allogeneic HCT

7. History of primary idiopathic myelofibrosis

8. MDS subjects may not receive RIC and must be < 50 years of age at the time of signing the informed consent form

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Regimen A (RIC: Flu/Cy/TBI)	Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Post-HCT Mesna	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Fludarabine	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Total Body Irradiation (TBI) 200cGy on Day -1	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Infusion of non-T-cell depleted bone marrow on Day 0	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	G-CSF	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Pre-HCT Mesna on Days -6 and -5	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Infusion of non-T-cell depleted bone marrow on Day 0	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Cyclophosphamide 50mg/kg/day IV on Days -2,-1	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Pre-HCT Mesna on Days -2 and -1	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Post-HCT Mesna	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	Fludarabine	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Post-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	Infusion of non-T-cell depleted bone marrow on Day 0	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	Busulfan	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	Post-HCT Mesna	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Infusion of non-T-cell depleted bone marrow on Day 0	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Cyclophosphamide 50mg/kg/day IV on Days -5,-4	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Sirolimus	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Post-HCT Mesna	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Mycophenolate mofetil	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Pre-HCT Mesna on Days -5 and -4	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Post-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	Post-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	Post-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Sirolimus	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen A (RIC: Flu/Cy/TBI)	Mycophenolate mofetil	1. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 2. Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 3. Total Body Irradiation (TBI) 200cGy on Day -1 4. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Busulfan	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Sirolimus	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	Mycophenolate mofetil	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2a (FIC: Bu/Cy)	G-CSF	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Cyclophosphamide 50mg/kg/day IV on Days -2,-1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	Mycophenolate mofetil	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	Sirolimus	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen B 2b (FIC: Bu/Flu)	G-CSF	1. Busulfan ≥ 9mg/kg total dose on Days -6, -5, -4, -3 (IV or PO) 2. Fludarabine 30 mg/m2/day IV on Days -6, -5, -4, -3, -2 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.
Regimen C (FIC: Cy/TBI)	G-CSF	1. Cyclophosphamide 50mg/kg/day IV on Days -5,-4 2. Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 3. Infusion of non-T-cell depleted bone marrow on Day 0 Although a schedule is proposed above, the regimen can be given according to institutional standards as long as the prescribed doses are the same as in the recommended regimen above.

Primary Outcome Measures

Name	Time	Method
Overall Survival	1 year post transplant

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	180 days and 365 days post-transplant
Transplant-related mortality	100 days, 180 days, and 365 days post-transplant
Cumulative incidence of neutrophil recovery	1 year post transplant
Cumulative incidence of platelet recovery	1 year post transplant
Cumulative incidence of primary graft failure	56 days post-transplant
Donor Chimerism	28 days, 56 days, 100 days, 180 days, and 365 days post-transplant	Peripheral blood chimerism (% of donor chimerism) in whole blood (unsorted)
Peripheral blood chimerism	56 days post-transplant	The percentage of subjects with peripheral blood (unsorted) chimerism\>95%
Cumulative incidence of acute GVHD	100 days post-transplant
Cumulative incidence of chronic GVHD	180 days and 365 days post-transplant
Cumulative incidences of viral reactivations and infections	100 days, 180 days and 365 days post-transplant
Cumulative incidence of relapse/progression	180 days and 365 days post-transplant
Cumulative incidences of thrombotic microangiopathy (TMA) and hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS)	1 year post transplant
Proportion of subjects proceeding to transplant	1 year post transplant
Donor Selection Characteristics	1 year post transplant	number of mismatches at HLA-A, -B, -C, -DRB1, -DQB1, -DPB1, donor age, donor-recipient CMV serostatus match, donor weight, donor-recipient sex match and donor-recipient ABO group match
Time from search to donor identification	1 year post transplant
Subgroup analysis of HIV-positive subjects	1 year post transplant	If CCR5delta32 homozygous donors are successfully found and used for one or more HIV-positive subjects, a descriptive analysis of baseline characteristics and outcomes for those HIV-positive subjects will be conducted, including the viral load detected over time obtained from collected samples.
Donor clonal hematopoiesis	100 days and 365 days post-transplant	The proportion of subjects developing donor clonal hematopoiesis

Trial Locations

Locations (11)

Memorial Sloan Kettering Cancer Center - Adults; 🇺🇸 New York, New York, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Virginia Commonwealth University Massey Cancer Center Bone Marrow Transplant Program; 🇺🇸 Richmond, Virginia, United States

University of Miami; 🇺🇸 Miami, Florida, United States

University of North Carolina Hospitals; 🇺🇸 Chapel Hill, North Carolina, United States

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

Shands HealthCare & University of Florida; 🇺🇸 Gainesville, Florida, United States

Froedtert Memorial Lutheran Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

University of Maryland Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Ohio State Medical Center, James Cancer Center; 🇺🇸 Columbus, Ohio, United States