Bone Marrow Transplant in Treating Patients With Hematologic Cancers

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00005797
First received: June 2, 2000
Last updated: October 24, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Multiple Myeloma and Malignant Plasma Cell Neoplasms
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Drug: busulfan
Drug: Cyclophosphamide
Drug: VP-16
Radiation: Fractionated Total Body Irradiation (FTBI)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Bone Marrow Transplantation for Hematologic Malignancies: A Treatment Approach Based on Risk of Relapse and Toxicity

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Relapse-free survival [ Time Frame: 5 years post transplant ] [ Designated as safety issue: No ]
    Relapse free survival 5 post transplant deteremiend by the Kaplan-Meier product-limit method.


Enrollment: 125
Study Start Date: March 1993
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
BuCy2
Busulfan & Cyclophosphamide
Drug: busulfan
administered on Day -7 through Day -4. The total dose is 12.8 mg/kg
Other Name: Busulfex®
Drug: Cyclophosphamide
administered at a dose of 60 mg/kg on each of two successive days (Days -3 and -2)
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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   15 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005797

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Study Chair: Teresa Field, MD, PhD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00005797     History of Changes
Other Study ID Numbers: MCC-11281, MCC-IRB-4188, NCI-G00-1759
Study First Received: June 2, 2000
Last Updated: October 24, 2012
Health Authority: United States: Federal Government

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
polycythemia vera
primary myelofibrosis
essential thrombocythemia
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
previously treated myelodysplastic syndromes
refractory cytopenia with multilineage dysplasia
chronic eosinophilic leukemia
chronic neutrophilic leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Additional relevant MeSH terms:
Leukemia
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms, Plasma Cell
Plasmacytoma
Preleukemia
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Disease
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Paraproteinemias
Pathologic Processes
Precancerous Conditions
Vascular Diseases
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 22, 2014