Trials / Completed

CompletedNCT00134004

Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer

A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Bone Marrow for Patients With Hematologic Malignancies

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 210 (actual)

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
Sex: All
Age: 6 Months – 74 Years
Healthy volunteers: Not accepted

Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and radiation therapy before a donor bone marrow transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.

Detailed description

OBJECTIVES: * Determine transplant-related mortality, risk of relapse, and progression-free survival of patients with standard- or high-risk hematologic malignancies undergoing nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by HLA-haploidentical allogeneic bone marrow transplantation. * Determine donor hematopoietic chimerism in patients' peripheral blood at 30, 60, and 180 days after transplantation. * Determine hematologic and nonhematologic toxic effects of this regimen in these patients. * Determine, when feasible, surface expression of HLA molecules and death receptors, sensitivity to cytotoxic lymphocytes, and expression of anti-apoptotic genes (e.g., Bcl-2, Bcl-xL, X-IAP, and c-FLIP) in cancer cells from patients who relapse after treatment with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to risk of relapse (standard \[defined as ≤ 30% risk\] vs high \[defined as ≥ 70% risk\]). * Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients undergo total body irradiation on day -1. * Allogeneic bone marrow transplantation: Patients undergo donor bone marrow infusion on day 0. * Post-transplantation therapy: Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. * Graft-vs-host disease prophylaxis: Beginning on day 5, patients receive oral mycophenolate mofetil 3 times daily until day 35 and tacrolimus IV (then changing to orally) twice daily until day 180. Treatment continues in the absence of disease progression. After completion of study transplantation, patients are followed on days 30, 60, 100, and 180; at 1 year; and then annually for 4 additional years. PROJECTED ACCRUAL: A total of 75-100 patients will be accrued for this study within 3-4 years.

Conditions

Interventions

Type	Name	Description
DRUG	cyclophosphamide
DRUG	fludarabine phosphate
DRUG	mycophenolate mofetil
DRUG	tacrolimus
PROCEDURE	allogeneic bone marrow transplantation
RADIATION	radiation therapy

Timeline

Start date: 2004-10-01
Primary completion: 2015-01-01
Completion: 2015-01-01
First posted: 2005-08-24
Last updated: 2015-10-06
Results posted: 2015-08-24

Locations

3 sites across 1 country: United States

Source: ClinicalTrials.gov record NCT00134004. Inclusion in this directory is not an endorsement.