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

August 5, 2010 updated by: Case Comprehensive Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I

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.
Drug: busulfan
Given orally
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
  • Enduxan
Procedure: allogeneic bone marrow transplantation
Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0.
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Drug: methylprednisolone
Given IV or orally
Other Names:
  • A-MethaPred
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: methotrexate
Given IV
Other Names:
  • Abitrexate
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclosporine
Given IV or orally
Other Names:
  • 27-400
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: obtained at least one month apart beginning no earlier than two month after marrow infusion
no evidence of leukemia as judged by two peripheral blood smears and two bone marrow aspirates and biopsies. Disease-free and overall survival data will be computed from the day of marrow infusion.
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
Time Frame: twice weekly
twice weekly

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Case Comprehensive Cancer Center

Investigators

  • Principal Investigator: Hillard Lazarus, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1988

Primary Completion (Actual)

February 1, 2000

Study Completion (Actual)

February 1, 2010

Study Registration Dates

First Submitted

August 5, 2010

First Submitted That Met QC Criteria

August 5, 2010

First Posted (Estimate)

August 9, 2010

Study Record Updates

Last Update Posted (Estimate)

August 9, 2010

Last Update Submitted That Met QC Criteria

August 5, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CWRU1494T
  • NCI-2010-01793

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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