NCT01349101

A Research Study of Bone Marrow Transplantation From Unrelated or Partially Matched Related Donors

Post Transplant Cyclophosphamide for Unrelated and Related Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

It is hypothesized that engraftment when administering cyclophosphamide post the stem cell infusion will increase, the incidence of graft versus host disease (GVHD) and day 100 mortality will decrease, and the use of cyclophosphamide post stem cell infusion with alternative donors will be as safe and as effective as traditional matched transplants.

Detailed description

The primary rationale for the development of this research study is to find out if the use of cyclophosphamide after a "blood" stem cell transplant is an effective treatment for patients with blood cancers who require transplant for long-term survival but are without an available matched-sibling donor. Historically, survival rates for patients undergoing partially matched related or unrelated donor transplants (henceforth to be called alternative donor transplants) have been much lower than those observed after matched sibling stem cell transplants. Survival post alternative donor stem cell transplant has also been affected by the requirement to remove or reduce the numbers of donor T cells resulting in higher rates of infection, graft rejection, and relapse. One significant limitation to conventional donor transplants with HLA matched siblings has been that over 50% of patients do not have HLA matched siblings so that increasing the safety of alternative donor transplants could have a significant influence on the number of patients who could safely receive transplants. Because of the historically low overall survival (OS) after alternative donor transplants, it has become a procedure of "last resort" in many centers unwilling to consider it unless all other options are exhausted. There fore several centers including ours have sought to overcome problems using various strategies. The strategy the investigators have proposed for this study (which has been used similarly by other centers) has been to administer cyclophosphamide post the stem cell infusion (traditionally it is given before the stem cell infusion) thereby hopefully destroying the activated T-cells causing graft-versus host disease (GVHD) and allow T cell tolerization and engraftment; but, not the inactivated T cells thereby hopefully preserving the anti-tumor effects of the donor immune system. Thus, the major aim of this study will be to measure the engraftment with this regimen and secondarily to measure incidence of GVHD and day 100 mortality. The goal is to see if in the first 3 months the use of cyclophosphamide post stem cell infusion with alternative donors is as safe and as effective as traditional matched transplants.

Conditions

• Hematological Malignancies

Interventions

Type	Name	Description
RADIATION	Total Body Irradiation	Myeloablative HSCT Arm: Total body irradiation (TBI) is given in 8 fractions over 4 days (total dose of 12 Gy) Reduced Intensity HSCT Arm: TBI is given in one fraction (total dose of 2 Gy)
DRUG	Cyclophosphamide	Cyclophosphamide is administered on the third day after the hematopoietic stem cell transplantation (HSCT) to help reduce graft-versus-host disease (GVHD). It is given at a dose of 60 mg/kg/d for 2 days on days +3 and +4.
DRUG	Tacrolimus	Started the fifth day after the transplant to help prevent graft-versus-host disease (GVHD).
DRUG	Mycophenolate mofetil	Started the fifth day after the transplant to help prevent graft-versus-host disease (GVHD).
DRUG	Fludarabine	Started the fifth day before the transplant. Given for four days at 30 mg/m2/d.
DRUG	Busulfan	Started the fourth day before the transplant. Given for two days at 3.2 mg/kg.
GENETIC	Hematopoietic stem cell transplantation	Allogeneic marrow transplantation given after the last dose of total body irradiation (TBI)

Timeline

• Start date: 2011-02-10
• Primary completion: 2022-10-31
• Completion: 2022-12-07
• First posted: 2011-05-06
• Last updated: 2025-12-15
• Results posted: 2025-12-15

Locations

1 site across 1 country: United States