Clinical Trial: Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Trial Combining Radiolabeled BC8 (Anti-CD45) Antibody With Fludarabine and Low Dose TBI Followed by Related or Unrelated PBSC Infusion and Post-Transplant Immunosuppression for Patients Wit

Brief Summary: This phase II trial studies the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given together with fludarabine phosphate, total-body irradiation, and donor stem cell transplant followed by cyclosporine and mycophenolate mofetil in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has spread to other places in the body and usually cannot be cured or controlled with treatment. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Also, radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving fludarabine phosphate and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together with donor stem cell transplant, cyclosporine, and mycophenolate mofetil may be an effective treatment for advanced acute myeloid leukemia or myelodysplastic syndromes.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the maximum tolerated dose (MTD) and the transplant-related mortality (TRM) and toxicity of delivering 131I-BC8 (iodine I 131 monoclonal antibody BC8) (anti-cluster of differentiation [CD]45 antibody) at a starting dose of 22 Gy to the normal organ receiving the highest dose in combination with the non-myeloablative regimen of fludarabine (fludarabine phosphate) (FLU), 2 Gy total body irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil (MMF), and human leukocyte antigen (HLA)-matched related or unrelated allogeneic hematopoietic stem cell transplant (HSCT) in patients 16 to 50 years old who have advanced acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS).

II. To estimate rates of donor chimerism resulting from this combined preparative regimen and to correlate level of donor chimerism with estimated radiation doses delivered to hematopoietic tissues via antibody.

III. To determine rates of disease relapse, graft vs. host disease, and 2-year disease-free survival in patients receiving 131I-BC8 antibody combined with FLU, 2 Gy TBI, CSP, MMF, and HLA-matched related or unrelated allogeneic HSCT.

OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.

RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 intravenously (IV) on day -12.

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: After completion of TBI, patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0.

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Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Incidence of dose-limiting toxicities to determine MTD of radiation delivered to normal organ by iodine I 131 monoclonal antibody BC8 [ Time Frame: Up to 100 days post-transplant ]

Escalation by 2 Gy increments will occur until a patient experiences a grade III/IV regimen-related toxicity (Bearman) or dose-limiting toxicity (DLT), at which point the second stage will begin at the next lower dose level. Estimated to be the dose that is associated with a toxicity rate of 25%.


Original Primary Outcome:

Current Secondary Outcome:

  • Rates of transplant-related mortality for patients receiving iodine I 131 monoclonal antibody BC8 when combined with 2 Gy TBI + CSP/MMF [ Time Frame: Up to 100 days post-transplant ]
    Descriptive statistics will be reported.
  • Disease response in patients receiving iodine I 131 monoclonal antibody BC8 combined with fludarabine phosphate, 2 Gy TBI, CSP, MMR and HLA-matched related or unrelated allogeneic HSCT [ Time Frame: Up to 11 years ]
  • Disease-free survival in patients receiving iodine I 131 monoclonal antibody BC8 combined with fludarabine phosphate, 2 Gy TBI, CSP, MMR and HLA-matched related or unrelated allogeneic HSCT [ Time Frame: Up to 2 years ]
    Kaplan-Meier estimates will be determined.
  • Rates of donor chimerism and graft-versus-host disease [ Time Frame: Days 28, 56, and 84 ]
    Variable number tandem repeat (VNTR) analysis or fluorescent in situ hybridization (FISH) studies will be used to quantitate chimerism. 95% confidence intervals will be reported.


Original Secondary Outcome:

Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: July 12, 2005
Date Started: May 2003
Date Completion:
Last Updated: April 13, 2017
Last Verified: April 2017