Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02

Masonic Cancer Center, University of Minnesota1 site in 1 country14 target enrollmentMarch 26, 2002

Interventionscyclophosphamide anti-thymocyte globulin filgrastim busulfan fludarabine phosphate methylprednisolone Hematopoietic stem cell transplantation

Drugsbusulfan cyclophosphamide fludarabine phosphate methylprednisolone

Overview

Phase: Phase 2
Intervention: cyclophosphamide
Conditions: Fanconi Anemia
Sponsor: Masonic Cancer Center, University of Minnesota
Enrollment: 14
Locations: 1
Primary Endpoint: Number of Participants Experiencing Graft Failure
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for patients with high risk Fanconi's anemia.

PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.

Detailed Description

OBJECTIVES: Primary * Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation. Secondary * Determine the tolerability of mycophenolate mofetil in these patients. * Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen. * Determine the incidence of major infections in patients with a history of major infections treated with this regimen. * Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen * Determine the probability of 1-year survival of patients treated with this regimen. OUTLINE: Patients are stratified according to donor/recipient HLA type (identical vs other). * Cytoreductive combination chemotherapy: Patients receive busulfan intravenously (IV) over 2 hours twice daily on days -7 and -6 and cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes once daily on days -5 to -2. * Graft failure prophylaxis: Patients receive methylprednisolone IV twice daily on days -5 to 30 and anti-thymocyte globulin IV over 4-6 hours twice daily on days -5 to -1. * Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -3 to 100 (if patient has a matched sibling donor) or days -3 to 180 (if patient has another donor type). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 45. * Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT (using bone marrow or umbilical cord blood) on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. After completion of study treatment, patients are followed periodically for 3 years.

Registry

clinicaltrials.gov

Start Date

March 26, 2002

End Date

October 10, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Masonic Cancer Center, University of Minnesota

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must be \<45 years of age with a diagnosis of Fanconi anemia with:
•Biallelic BRCA2 mutations, or
•Aplastic anemia, or advanced myelodysplastic syndrome (MDS) (MDS with ≥5% blasts), or acute leukemia who are ineligible for total body irradiation. Aplastic anemia is defined as having at least one of the following (with or without cytogenetic abnormalities): platelet count \<20 \* 10\^9, - absolute neutrophil count (ANC) \<5 \* 10\^8/L, - Hgb \<8 g/dL
•Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors will be typed for HLA-A and B using serological level typing and for DRB1 using high resolution molecular typing.
•Adequate major organ function including:
•Cardiac: ejection fraction \>45%
•Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites, no cirrhosis)
•Karnofsky performance status \>70% or Lansky \>50%
•Women of child bearing potential must be using adequate birth control and have a negative pregnancy test.

Exclusion Criteria

•Active CNS leukemia at time of HSCT.
•Active uncontrolled infection within one week of hematopoietic stem cell transplant (HSCT).
•Pregnant or lactating female.
•Donor Inclusion Criteria:
•Donor must be in good health based on review of systems and results of physical examination.
•Donor must have a normal hemoglobin, white count, platelet count and partial thromboplastin time (PTT), and a negative diepoxybutane (DEB) test.
•HIV-NAT negative, HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
•Female donors of childbearing potential must have a negative pregnancy test.
•Unrelated donors must agree to peripheral blood stem cell (PBSC) donation
•Donor Exclusion Criteria:

Intervention: Hematopoietic stem cell transplantation

Outcomes

Primary Outcomes

Number of Participants Experiencing Graft Failure

Time Frame: Day 30

Graft failure is defined as absolute neutrophil count( ANC ) \<5 x 10\^8/L by day 30.

Secondary Outcomes

Number of Participants Experiencing Acute Graft-Versus-Host Disease(Day 42)
Number of Participants Experiencing Relapse(1 Year)
Number of Participants Experiencing Overall Survival(1 Year)
Number of Participants Experiencing Major Infections(Day 1 through 1 year post-transplant)
Number of Participants Experiencing Chronic Graft-Versus-Host Disease(1 year)