HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation With Reduced Dose Post Transplantation Cyclophosphamide GvHD Prophylaxis

Summary

The goal of this clinical trial is to determine the effectiveness of Reduced Dose Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question\[s\] it aims to answer are:

* Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant?
* Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Acute Leukemia
• Myelodysplastic Syndromes
• Chronic Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Myeloproliferative Neoplasm
• Lymphoma
• Chronic Myelomonocytic Leukemia
• Pro-Lymphocytic Leukemia
• Myelofibrosis

Interventions

DRUG

Cyclophosphamide

Given IV pre-transplant as part of conditioning regimen

DRUG

Mesna

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

DRUG

Melphalan

Given IV pre transplant as part of conditioning regimen

RADIATION

Total-body irradiation

Administered pre-transplant as part of conditioning regimen

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 Day + 90 and finished by Day +180.

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 transplant, at Day + 100, Day + 180, and Day +365 post transplant.

DRUG

Busulfan

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

DRUG

Fludarabine

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

DRUG

Post-Transplant Cyclophosphamide

Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours. First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 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

• Jeffery Auletta, MD · NMDP

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-08

Primary Completion

2026-02-01

Completion

2026-06-30

Countries

• United States

Study Locations