NCT00988715

Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

Hematopoietic Cell Transplantation for Patients With High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Radiolabeled DOTA-Biotin Pretargeted by BC8 Antibody-Streptavidin Conjugate

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies pretargeted radioimmunotherapy and donor peripheral blood stem cell transplant employing fludarabine phosphate and total-body irradiation (TBI) to treat patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Giving chemotherapy drugs, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies can be combined with fludarabine phosphate and TBI to find cancer cells and kill them without harming normal cells. Pretargeted radioimmunotherapy (PRIT) allows for further improved targeting of tumor cells over standard directly labeled antibodies.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) of radiation delivered via PRIT using BC8-SA (BC8 antibody-streptavidin conjugate) when combined with fludarabine (FLU) (fludarabine phosphate), 2 Gy total body irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil (MMF), and allogeneic hematopoietic cell transplant (HCT) in patients who have advanced acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or high risk myelodysplastic syndromes (MDS). SECONDARY OBJECTIVES: I. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting from this combined preparative regimen. II. To estimate rates of disease relapse, acute graft-versus-host disease (GvHD), and day-100 disease-free survival in patients receiving PRIT using BC8-SA combined with FLU, 2 Gy TBI, CSP, MMF, and allogeneic HCT. III. To assess biodistribution, serum half-life, urinary excretion, tissue localization, and clearance of BC8-SA conjugate and DOTA-biotin. IV. To assess the feasibility of yttrium y 90 (90Y)-DOTA-biotin to bind to BC8-SA conjugate localized to hematolymphoid tissues. OUTLINE: Patients undergo pretargeted radioimmunotherapy comprising a test dose of BC8-SA conjugate intravenously (IV) on day -22 and indium In 111(111In)-DOTA-biotin IV on day -20, followed by a therapy dose of BC8-SA conjugate IV on day -14 and 90Y-DOTA-biotin IV on day -12. Patients receive fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and then peripheral blood stem cell transplantation on day 0. Patients with matched related donors receive cyclosporine IV on days -3 to 56 and taper to day 180 and mycophenolate mofetil orally (PO) twice daily (BID) on days 0-27. Patients with matched unrelated donors receive cyclosporine IV on days -3 to 100 and taper to day 180 and mycophenolate mofetil PO thrice daily (TID) on days 0-40 and taper to day 96. After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months, and then annually thereafter.

Conditions

• Chronic Myelomonocytic Leukemia
• Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
• Previously Treated Myelodysplastic Syndrome
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Refractory Anemia With Excess Blasts
• Refractory Cytopenia With Multilineage Dysplasia
• Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts
• Secondary Acute Myeloid Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Pretargeted Radioimmunotherapy	Antibody-streptavidin conjugate and radiolabeled DOTA-biotin, each given IV
DRUG	Cyclosporine	Given IV
DRUG	Mycophenolate Mofetil	Given PO
RADIATION	Total-Body Irradiation	Undergo total-body irradiation
PROCEDURE	Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation	Undergo peripheral blood stem cell transplant
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo peripheral blood stem cell transplant
DRUG	Fludarabine Phosphate	Given IV
OTHER	Pharmacological Study	Correlative studies
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2010-04-21
• Primary completion: 2015-01-01
• First posted: 2009-10-02
• Last updated: 2017-08-30

Locations

1 site across 1 country: United States