NCT00589316

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

Hematopoietic Bone Marrow Transplantation for Patients With High-risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Related HLA-Mismatched Donors: A Trial Using Radiolabeled Anti-CD45 Antibody Combined With Immunosuppression Before and After Transplantation

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of iodine I 131monoclonal antibody BC8 when given together with fludarabine phosphate, cyclophosphamide, total-body irradiation, and donor bone marrow transplant, and to see how well they work in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia that has spread to nearby or other places in the body (advanced), or high-risk myelodysplastic syndrome. Giving chemotherapy drugs, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow 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 cyclophosphamide together with mycophenolate mofetil and tacrolimus after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together with donor stem cell transplant, fludarabine phosphate, cyclophosphamide, mycophenolate mofetil, and tacrolimus may be an effective treatment for advanced acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose of radiation delivered via 131 I-BC8 antibody (iodine I 131 monoclonal antibody BC8) when combined with pre- and post-transplant cyclophosphamide (CY), fludarabine phosphate (FLU), 2 Gy total-body irradiation (TBI), tacrolimus, mycophenolate mofetil (MMF), and a haploidentical allogeneic hematopoietic marrow transplant in patients who have advanced acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or high risk myelodysplastic syndromes (MDS). II. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting from this combined preparative regimen. III. To determine rates of disease relapse, acute graft-versus-host disease (GVHD), and day 100 disease-free survival in patients receiving 131 I-BC8 antibody (Ab) combined with CY, FLU, 2 Gy TBI, tacrolimus, MMF, and human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic cell transplant (HCT). OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8. RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 via central line on day -14. NONMYELOABLATIVE CONDITIONING: Patients receive FLU intravenously (IV) over 30 minutes on days -6 to -2 and CY IV over 1 hour on days -6 and -5. Patients undergo TBI on day -1. TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0. POST-TRANSPLATATION IMMUNOSUPPRESSION: Patients receive CY IV over 1-2 hours on day 3, MMF IV or orally (PO) thrice daily (TID) on days 4 to 35, and tacrolimus IV over 1-2 hours or PO on days 4 to 180 with taper on day 84. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months, and then annually thereafter.

Conditions

• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Adult Acute Lymphoblastic Leukemia in Remission
• Adult Acute Myeloid Leukemia in Remission
• CD45-Positive Neoplastic Cells Present
• Chronic Myelomonocytic Leukemia
• Previously Treated Myelodysplastic Syndrome
• Refractory Anemia With Excess Blasts
• Refractory Anemia With Ring Sideroblasts
• Refractory Cytopenia With Multilineage Dysplasia
• Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Bone Marrow Transplantation	Given via central line
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine Phosphate	Given IV
RADIATION	Iodine I 131 Monoclonal Antibody BC8	Given IV (dosimetry dose) or via central line (therapeutic dose)
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Mycophenolate Mofetil	Given IV or PO
DRUG	Tacrolimus	Given IV or PO
RADIATION	Total-Body Irradiation	Undergo TBI

Timeline

• Start date: 2007-10-05
• Primary completion: 2016-10-01
• Completion: 2021-10-01
• First posted: 2008-01-09
• Last updated: 2023-02-09
• Results posted: 2023-02-09

Locations

1 site across 1 country: United States