High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

High-dose Busulfan, High-dose Cyclophosphamide, and Allogeneic Bone Marrow Transplantation for Leukemia, Myelodysplastic Syndromes, Multiple Myeloma and Lymphoma

Sponsors

Lead Sponsor: Case Comprehensive Cancer Center

Source Case Comprehensive Cancer Center
Brief Summary

RATIONALE: Giving high doses of chemotherapy drugs, such as busulfan and cyclophosphamide, 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methylprednisolone, and methotrexate after transplant may stop this from happening. PURPOSE: This clinical trial studies high-dose busulfan and high-dose cyclophosphamide followed by donor bone marrow transplant in treating patients with leukemia, myelodysplastic syndrome, multiple myeloma, or recurrent Hodgkin or Non-Hodgkin lymphoma.

Detailed Description

OBJECTIVES: I. To determine the toxicity and efficacy of the high-dose chemotherapy regimen which employs busulfan, cyclophosphamide, and allogeneic bone marrow transplantation. II. To ascertain feasibility (safety) and efficacy of the use of intensive chemotherapy regimen (busulfan and cyclophosphamide) followed by allogeneic bone marrow transplantation in patients with leukemia, myelodysplastic syndromes, multiple myeloma, and lymphoma. OUTLINE: HIGH-DOSE CHEMOTHERAPY: Patients receive oral busulfan every 6 hours on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 and -3, or -4 to -2 . TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine IV over 6 hours on day -1, over 10 hours twice daily on days 0-20, and then orally every 12 hours beginning on day 21 and continuing for 12 months with taper at 9 months. Patients also receive methylprednisolone IV or orally beginning on day 8 and continuing for 7 months with taper at 4 months. Some patients may also receive methotrexate IV on days 1, 3 and 6 . After completion of study treatment, patients are followed up periodically.

Overall Status Completed
Start Date 1988-03-01
Completion Date 2010-02-01
Primary Completion Date 2000-02-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Response rate obtained at least one month apart beginning no earlier than two month after marrow infusion
Toxicity as assessed by NCI CTC and engraftment (bone marrow) toxicity criteria twice weekly
Enrollment 13
Condition
Intervention

Intervention Type: Drug

Intervention Name: busulfan

Description: Given orally

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: cyclophosphamide

Description: Given IV

Arm Group Label: Arm I

Intervention Type: Procedure

Intervention Name: allogeneic bone marrow transplantation

Description: Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0.

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: methylprednisolone

Description: Given IV or orally

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: methotrexate

Description: Given IV

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: cyclosporine

Description: Given IV or orally

Arm Group Label: Arm I

Eligibility

Criteria:

Criteria - Acute non-lymphocytic leukemia (FAB types M1-M7) in first, or second remission, or early first or second bone or marrow relapse (>31% marrow blasts and no circulating peripheral blasts) - All patients with acute promyelocytic leukemia in first complete remission who have received retinoic acid and chemotherapy are not eligible - Acute lymphocytic leukemia in first or second remission, or early first or second bone marrow relapse (31% marrow blasts and no circulating peripheral blasts) - Pediatric ALL patients in first complete remission are not eligible - Chronic myelogenous leukemia in first or second chronic phase, or accelerated phase - Myelodysplastic syndrome =< 50 years - Lymphoma patients age =< 50 years (non Hodgkins or Hodgkins) in first or second relapse, or refractory disease, who are ineligible for autologous bone marrow transplantation because of tumor in the bone marrow - Multiple myeloma patients age =< 50 who have relapsed or are refractory to at least 2 chemo-radiation or chemotherapy regimens - Patients who have failed a previous allogeneic bone marrow transplant - Patients with inborn errors of metabolism - ECOG performance status of 0 or 1 - Karnofsky performance status of >= 70% - Patients must be HTLV-III (HIV) anti-body negative - Acute and chronic leukemia patients must be age =< 50 years; patients up to age 60 years for any of these diseases who have a syngeneic donor are eligible - Patients (or bone marrow donors) who are HTLV-III (HIV) antibody positive are ineligible for this study - Patients must not have active infection - Patients must not have cytotoxic chemotherapeutic agents for at least 4 weeks before the transplant conditioning regimen is to begin - It is recommended but not required that acute leukemia patients undergoing transplantation in first remission must have received at least one course of consolidation therapy - Patients undergoing transplant in early relapse are eligible for transplant in first and second relapse only - Patients must have no history of acute myocardial infarction in the 6 months prior to transplantation, angina pectoris requiring nitrate therapy, uncontrolled major ventricular dysrhythmia, uncontrolled hypertension, or uncontrolled congestive heart failure - A gated-pool radionuclide scan fraction must be >= 50% - Serum creatinine must be =< 1.8% and a 24 hour creatinine clearance must be >= 60ml/min - Serum direct bilirubin >= 1.8mg%, or serum SGOT or SGPT > twice normal will exclude patients from this study - Severe symptomatic CNS disease of any etiology other than CNS leukemia will exclude patients from study - FEV1 and DLco (corrected) must be >= 60% of normal - pO2 > 60mmHg - Insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction render patients ineligible - Written informed consent must be obtained - Patients treated previously with radiation therapy in excess of 1000 cGy (rads) to any thoracic or abdominal port, or in excess of 3000 cGy (rads) to cranial-spinal ports, who are not eligible for other protocols are eligible for this study - DONOR: All genotypically HLA- or D/DR identical siblings are eligible to be bone marrow donors so long as their general medical condition permits the safe use of general or spinal anesthesia; selected donors who are not HLA-identical may be considered for use as long as they are D/DR identical, MLC compatible, and are in good condition to safely undergo spinal or general anesthesia - DONOR: This protocol will allow the use of donors who are unrelated but are HLA-A, b, C, D/Dr identical and MLC (mixed lymphocyte culture) compatible - Patient must have adequate insurance to cover the cost of the transplant and hospitalization

Gender:

All

Minimum Age:

N/A

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Hillard Lazarus Principal Investigator Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Location
Facility: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Location Countries

United States

Verification Date

2010-08-01

Responsible Party

Name Title: Lazarus, Hillard

Organization: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Arm I

Type: Experimental

Description: HIGH-DOSE CHEMOTHERAPY: Patients receive oral busulfan every 6 hours on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 and -3, or -4 to -2. TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine IV over 6 hours on day -1, over 10 hours twice daily on days 0-20, and then orally every 12 hours beginning on day 21 and continuing for 12 months with taper at 9 months. Patients also receive methylprednisolone IV or orally beginning on day 8 and continuing for 7 months with taper at 4 months. Some patients may also receive methotrexate IV on days 1, 3 and 6.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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