Bone Marrow Transplant in Treating Patients With Hematologic Cancers

December 9, 2020 updated by: H. Lee Moffitt Cancer Center and Research Institute

Allogeneic Bone Marrow Transplantation for Hematologic Malignancies: A Treatment Approach Based on Risk of Relapse and Toxicity

RATIONALE: Giving chemotherapy drugs and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps 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.

PURPOSE: This phase II trial is studying how well donor bone marrow transplant works in treating patients with hematologic cancers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the progression free survival (PFS) and overall survival (OS) of patients with low risk myeloid disorders or older allogeneic recipients who are treated with high dose busulfan and cyclophosphamide and allogeneic bone marrow transplantation (BMT).
  • Determine the PFS and OS in patients with lymphoid and high risk myeloid disorders who are treated with etoposide, total body irradiation, and allogeneic BMT.
  • Evaluate the toxicities of these 2 regimens when combined with cyclosporine and methotrexate as graft versus host disease prophylaxis in these patients.
  • Evaluate the PFS and OS of allogeneic BMT in patients with multiple myeloma and chronic lymphocytic leukemia.

OUTLINE:

  • Regimen A: Patients with chronic myelogenous leukemia (CP1, AP/CP2) and other myeloproliferative disorders, myelodysplastic disorders, acute myelogenous leukemia (CR1), or multiple myeloma (not eligible to receive total body irradiation due to prior radiation) are treated with high dose busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation (BMT). Patients receive oral busulfan every 6 hours on days -7 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Allogeneic bone marrow is infused on day 0.
  • Regimen B: Patients with acute myelogenous leukemia (at least CR2, relapsed), acute lymphoid leukemia (ALL), any acute leukemia with CNS involvement, multiple myeloma, or chronic lymphocytic leukemia are treated with total body irradiation and etoposide followed by allogeneic BMT. Patients receive total body irradiation (TBI) on days -7 to -4 for a total of 11 fractions and etoposide IV over 4 hours on day -3. Male patients with ALL receive a testicular boost in 2 fractions on 2 successive days during TBI. Allogeneic bone marrow is infused on day 0.

Patients in both regimens receive cyclosporine and methotrexate as graft versus host disease prophylaxis.

Patients are followed weekly for 3 months and then monthly for 1 year.

PROJECTED ACCRUAL: At least 50 patients with low risk myeloid disease, 50 patients with lymphoid malignancies, and 60 patients with high risk myeloid disease will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

125

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
    • Florida
      • Tampa, Florida, United States, 33612-9497
        • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

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

15 years to 55 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of:

    • Acute myelogenous leukemia

      • Complete remission (CR) 1 - ALL except good cytogenetics defined as [(inv16, t(8,21), t(15,17)]
      • CR2
      • Induction failures
      • Relapsed OR

    • Acute lymphocytic leukemia (ALL)

      • CR1 - high risk defined as overt CNS involvement, 1 or more risk factors (age 30 and over, WBC at least 20,000/mm^3, at least 4 weeks to CR1, myeloid phenotype)
      • CR2
      • Induction failures
      • Relapsed OR

    • Chronic myelogenous leukemia

      • Chronic phase (CP) 1
      • Accelerated phase (AP)/CP2 OR

    • Chronic lymphocytic leukemia

      • At diagnosis - RAI stage III/IV or Binet C

        • Must undergo 1 induction regimen

      • Relapsed - any stage

        • Must have received no more than 3 regimens for diagnosis OR

    • Multiple myeloma

      • At diagnosis - stage II/III (primary refractory or sensitive)
      • Relapsed no more than 2 times - sensitive disease
      • Plasma cell leukemia OR

    • Myelodysplasia

      • All subtypes eligible OR

    • Myeloproliferative disorders

      • Poor response to medical therapy OR
      • Cytogenetic abnormalities

  • Must have a related donor who is genotypic 6 out of 6 HLA A, B, and DR match

    • Molecular DR matching required

PATIENT CHARACTERISTICS:

Age:

  • 15 to 55

Performance status:

  • Karnofsky 80-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • SGOT/SGPT no greater than 3 times upper limit of normal
  • PT/PTT normal

Renal:

  • Creatinine no greater than 2.0 mg/dL
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • LVEF at least 45% by MUGA scan or echocardiography
  • No myocardial infarction within the past 6 months
  • No arrhythmias controlled by therapy

Pulmonary:

  • FEV_1 at least 50% predicted
  • DLCO at least 50% predicted

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • No diabetes mellitus or thyroid disease that is not medically controlled
  • No psychosocial disorder that would preclude study compliance
  • No active serious infections
  • HIV negative
  • Donor must be HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

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: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: BuCy2
Busulfan & Cyclophosphamide
Drug: busulfan
administered on Day -7 through Day -4. The total dose is 12.8 mg/kg
Other Names:
  • Busulfex®
Drug: Cyclophosphamide
administered at a dose of 60 mg/kg on each of two successive days (Days -3 and -2)
OTHER: VP16/TBI
Fractionated Total Body Irradiation + VP-16
Drug: VP-16
administered as a single infusion on Day -3. The dose is 60 mg/kg and is calculated on actual body weight unless the patient's weight is >/= 150% of IBW, in which case adjusted body weight will be used.
Other Names:
  • Etoposide (VP-16; Vepesid(R) brand only)
Radiation: Fractionated Total Body Irradiation (FTBI)
FTBI is performed on day -7 through day -4. The total dose of radiation is 1,320 cGy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse-free survival
Time Frame: 5 years post transplant
Relapse free survival 5 post transplant deteremiend by the Kaplan-Meier product-limit method.
5 years post transplant

Collaborators and Investigators

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

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

National Cancer Institute (NCI)

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, 1993

Primary Completion (ACTUAL)

July 1, 2007

Study Completion (ACTUAL)

July 1, 2007

Study Registration Dates

First Submitted

June 2, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ACTUAL)

December 10, 2020

Last Update Submitted That Met QC Criteria

December 9, 2020

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-11281
  • MCC-IRB-4188 (OTHER: University of South Florida)
  • NCI-G00-1759 (OTHER_GRANT: NCI)

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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