NCT00303719

Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 342 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 75 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.

Detailed description

OBJECTIVES: * Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and durable donor engraftment in patients with hematologic malignancies or kidney cancer who are undergoing allogeneic stem cell transplantation. * Determine the safety of this nonmyeloablative transplantation regimen in these patients. * Determine the risk of graft-versus-host-disease in patients treated with this regimen. * Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in patients treated with this regimen. * Determine the effect of lower doses of daily fludarabine on treatment-related mortality (TRM) OUTLINE: Patients are stratified according to risk (standard vs high). * Preparative regimen\*: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)\*\* IV every 12 hours on days -6 to -4. Patients who receive ATG\* include the following: * Related donor recipients who have not received combination chemotherapy within the past 6 months * Unrelated donor recipients who have not received combination chemotherapy within the past 3 months * Unrelated donor recipients who have received only 1 induction course for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or blastic phase chronic myelogenous leukemia (CML) NOTE: \*\*Patients who underwent prior autologous stem cell transplantation in the past year do not receive ATG. * Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. * Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours beginning on day -3 and continuing until at least day 100. Patients also receive mycophenolate mofetil IV or orally twice daily on days -3 to 30. * Donor lymphocyte infusion (DLI): Patients without active GVHD but deteriorating donor chimerism may receive DLI IV over 2 hours. After completion of study treatment, patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Conditions

• Kidney Cancer
• Leukemia
• Lymphoma
• Multiple Myeloma
• Plasma Cell Neoplasm
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
BIOLOGICAL	anti-thymocyte globulin	ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4. Those that should/will receive ATG in the preparative regimen: * Related donor recipients who have not had exposure to combination chemotherapy in the 6 months preceding transplant should * Unrelated donor recipients who have not had exposure to combination chemotherapy in the 3 months preceding transplant will * Unrelated donor recipients who have had only a single induction cycle for the treatment of ALL/AML or MDS or CML blast crisis should * Recipients with a prior autologous transplant in the year prior to second transplant do not require ATG.
DRUG	cyclophosphamide	Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.
DRUG	cyclosporine	Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of \>200. For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours. Patients will receive CSA until day +100.
DRUG	fludarabine	Fludarabine 30 mg/m\^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m\^2 for 5 days.
DRUG	mycophenolate mofetil	Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if \< 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) \> 0.5 x 109 /L).
PROCEDURE	stem cell transplantation	On day 0, if related donor, stem cells are infused via central line. If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.
RADIATION	total body irradiation	The dose of TBI will be 200 cGy given in a single fraction on day -1.
DRUG	filgrastim	Patients with white blood cell (WBC) counts \< 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) \> 2500 for 2 consecutive days.

Timeline

• Start date: 2002-03-26
• Primary completion: 2019-05-08
• Completion: 2019-05-08
• First posted: 2006-03-17
• Last updated: 2020-05-12
• Results posted: 2020-05-12

Locations

1 site across 1 country: United States