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

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.

Conditions

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

Interventions

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.

Sponsors & Collaborators

• Baptist Health South Florida

  lead OTHER

Principal Investigators

• Guenther Koehne, MD · Miami Cancer Institute (MCI) at Baptist Health, Inc.

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

74 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-09-30

Primary Completion

2030-03-01

Completion

2030-03-01

FDA Device

Yes

Countries

• United States

Study Locations