NCT00789776

Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer

A Phase I/II Study Evaluating the Safety and Efficacy of Adding a Single Prophylactic Donor Lymphocyte Infusion (DLI) of Natural Killer Cells Early After Nonmyeloablative, HLA-Haploidentical Hematopoietic Cell Transplantation - A Multi Center Trial

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of donor natural killer (NK) cell therapy and to see how well it works when given together with fludarabine phosphate, cyclophosphamide, total-body irradiation, donor bone marrow transplant, mycophenolate mofetil, and tacrolimus in treating patients with hematologic cancer. Giving chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem 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. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving mycophenolate mofetil and tacrolimus after the transplant may stop this from happening.

Detailed description

PRIMARY OBJECTIVES: I. Identification of the maximal feasible dose of NK cells that can be infused one week after nonmyeloablative, human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplant (HCT). (Phase I) SECONDARY OBJECTIVES: Once the maximal feasible dose has been identified, accrual will be limited to the cohort containing this cell dose to determine: I. Incidence of relapse. (Phase II) II. Incidence of grades III-IV acute graft-versus-host disease (GVHD). (Phase II) III. Incidence of non-relapse mortality. (Phase II) OUTLINE: This is a phase I, dose-escalation study of donor NK cell therapy followed by a phase II study. CONDITIONING: Patients receive fludarabine intravenously (IV) over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total-body irradiation on day -1. DONOR BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0. POST-TRANSPLANTATION IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3 and mycophenolate mofetil orally (PO) thrice daily (TID) on days 4 to 40, followed by a taper until day 84 in the absence of GVHD. Patients also receive tacrolimus IV continuously or IV once daily (QD) over 1-2 hours or PO twice daily (BID) on days 4 to 84, followed by a taper until day 180 in the absence of GVHD. DONOR NK CELL INFUSION: Patients undergo donor lymphocyte infusion of NK cells on day 7. After completion of study treatment, patients are followed up at 6 months, 1 year, 1.5 years, and then every year thereafter.

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Aggressive Non-Hodgkin Lymphoma
• Diffuse Large B-Cell Lymphoma
• Previously Treated Myelodysplastic Syndrome
• Recurrent Chronic Lymphocytic Leukemia
• Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Recurrent Indolent Adult Non-Hodgkin Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Plasma Cell Myeloma
• Recurrent Small Lymphocytic Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Refractory Hodgkin Lymphoma
• Refractory Plasma Cell Myeloma
• Refractory Small Lymphocytic Lymphoma
• Waldenstrom Macroglobulinemia

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Bone Marrow Transplantation	Undergo donor bone marrow transplantation
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Mycophenolate Mofetil	Given PO
BIOLOGICAL	Natural Killer Cell Therapy	Given IV
DRUG	Tacrolimus	Given IV or PO
RADIATION	Total-Body Irradiation	Undergo total-body irradiation

Timeline

• Start date: 2008-10-13
• Primary completion: 2017-05-01
• Completion: 2017-05-01
• First posted: 2008-11-13
• Last updated: 2020-01-31
• Results posted: 2018-07-12

Locations

3 sites across 1 country: United States