HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide

Summary

This is a prospective, multi-center, Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated donors (MMUD) for peripheral blood stem cell transplant in adults and bone marrow stem cell transplant in children. Post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil (MMF) will be used for for graft versus host disease (GVHD) prophylaxis. This trial will study how well this treatment works in patients with hematologic malignancies.

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myelogenous Leukemia
• Mixed Phenotype Acute Leukemia
• Acute Leukemia
• Myelodysplastic Syndromes
• Chronic Myelogenous Leukemia
• Chronic Lymphocytic Leukemia
• Lymphoma

Interventions

DRUG

Busulfan

Given IV or PO pre-transplant as part of conditioning regimen

DRUG

Busulfan

Given IV pre-transplant as part of conditioning regimen

DRUG

Fludarabine

Given IV pre-transplant as part of conditioning regimen

RADIATION

Total-body irradiation

Administered pre-transplant as part of conditioning regimen

DRUG

Cyclophosphamide

Given IV pre-transplant as part of conditioning regimen

DRUG

Melphalan

Given IV pre-transplant as part of conditioning regimen

PROCEDURE

PBSC Hematopoietic Stem Cell Transplantation (HSCT)

Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0.

PROCEDURE

Bone Marrow Hematopoietic Stem Cell Transplantation

Bone marrow graft is infused from a mismatched unrelated donor on Day 0.

DRUG

Post-transplant Cyclophosphamide

Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.

DRUG

Mesna

Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.

DRUG

Tacrolimus

Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

DRUG

Mycophenolate Mofetil

Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.

OTHER

Patient-Reported Outcomes

Survey assessments will be administered to study participants pre- and post-transplant.

Sponsors & Collaborators

• National Marrow Donor Program

  collaborator OTHER

• Center for International Blood and Marrow Transplant Research

  lead NETWORK

Principal Investigators

• Steven Devine, MD · NMDP/Be The Match

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Year

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-09-30

Primary Completion

2026-08-31

Completion

2026-12-31

Countries

• United States

Study Locations