NCT04282174

CD34+ Enriched Transplants From HLA-Compatible Patients With Hematologic Malignancies

A Phase II Trial of CD34+ Enriched Transplants From HLA-Compatible Related or Unrelated Donors for Treatment of Patients With Hematologic Malignancies

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Baptist Health South Florida · Academic / Other
• Sex: All
• Age: 74 Years
• Healthy volunteers: Accepted

Summary

This is a Phase II trial testing disease-specific myeloablative conditioning regimens for preparatory cytoreduction of patients receiving allogeneic HLA-compatible related or unrelated transplants of GCSF-mobilized peripheral blood stem cells (PBSC) depleted of T-cells by positive selection of CD34+ progenitor cells using the CliniMACS system. The CliniMACS Fractionation system is a method that positively selects CD34+ progenitor cells from PBSC by immunoadsorption of cells binding on anti CD34 monoclonal antibody to paramagnetic beads, which can then be isolated by passage through a magnetized column and released by agitation of beads. Two conditioning regimens have been used successfully with an alternative similar system, isolex, which is no longer being manufactured.

Detailed description

For this trial, patients will be put into one of two myeloablative conditioning regimens, based on their disease, stage of disease, and dose of radiation accumulated in the course of treatment. Approximately twenty-four to forty-eight hours after completion of each conditioning regimen, patients will receive a transplant of a CD34+ progenitor cell-enriched, T-cell depleted fraction of GCSF-mobilized PBSC after fractionation on the CliniMACS device, from his/her HLA compatible donor. Due to stringent T-cell depletion, no significant Graft-versus-host disease is anticipated. Should Graft-versus-host disease occur, standard treatment would be initiated per the Transplant Service guidelines. The purpose of this trial is to evaluate the potential of T-cell depleted Haploidentical Stem Cell Transplant fractionated by the CliniMACS system, when administered for disease targeted cytoreductive regimens, to secure consistent engraftment and hematopoietic reconstitution in HLA-compatible related or unrelated hosts, and to prevent or abrogate acute and chronic forms of Graft-versus-host disease. This study seeks to validate that these pre-transplant conditioning regimens, when administered with a CD34+ progenitor cell enriched, T-cell depleted graft, fractionated in the CliniMACS system, will be associated with a low incidence of non-leukemic mortality. The sample size is as follows: Regimen A: Hyperfractionated Total Body Irradiation/Thiotepa/Cyclophosphamide: 100 patients Regimen B: Busulfan/Melphalan/Fludarabine: 100 patients It is anticipated that the accrual will last five years. Patients will be followed for two years following transplantation.

Conditions

• Hematologic Diseases
• Hematologic Malignancy
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Myelogenous Leukemia
• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DEVICE	CliniMACS	allogeneic Human leukocyte antigen-compatible related or unrelated transplants of GCSF-mobilized peripheral blood stem cells depleted of T-cells by positive selection of CD34+ progenitor cells using the CliniMACS system
PROCEDURE	Bone Marrow Transplant	Bone Marrow Transplant will come from either an HLA matched related sibling or HLA un-related donor
DRUG	Hyperfractionated Total Body Irradiation	Hyperfractionated Total Body Irradiation is administered at a dose rate of \< 20 cGy/minute. Doses of 125 cGy/fraction are administered at a minimum interval of 4 hours between fractions, three times/day for a total of 11 or 12 doses (1375 or 1500 cGy) over 4 days (Day -9, -8, -7 and -6).
DRUG	Thiotepa	Thiotepa: 5mg/kg/day IV over approximately 4 hr. daily x 2 (Day -5 and Day -4). If scheduling of transplant harvests requires, the dose of Thiotepa may be administered as a single dose of 10mg/kg/day x 1.
DRUG	Cyclophosphamide	Cyclophosphamide: 60 mg/kg/day I V over approximately 30 min daily x 2 days (d -3 and -2). Cyclophosphamide dosing will be adjusted if patient is \> 125% of ideal body w eight and will be calculated based on adjusted ideal body weight, as per MCI standard of care guidelines.
DRUG	Busulfan	0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified
DRUG	Melphalan	Melphalan 70mg/m2/day x 2 days IV over 30 minutes. Dose should be adjusted if patient is \> 125% ideal body weight and should be calculated on adjusted ideal body weight per MCI standard of care guidelines. Melphalan will be administered on Days - 7 and -6 for multiple myeloma patients.
DRUG	Fludarabine	Fludarabine 25mg/m2/days x 5 days IV over 30 minutes. Fludarabine may be adjusted in the case of renal toxicity. In select cases in which the peripheral blood stem cells must be harvested a day later than requested due to a scheduling issue with the donor or Stem Cell Processing Laboratory.

Timeline

• Start date: 2022-09-01
• Primary completion: 2030-03-01
• Completion: 2030-03-01
• First posted: 2020-02-24
• Last updated: 2022-09-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study