Bone Marrow Transplant in Treating Patients With Hematologic Cancers - Full Text View

Sponsors and Collaborators:	H. Lee Moffitt Cancer Center and Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00005797

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 Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: etoposide Drug: methotrexate Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	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 National Cancer Institute (NCI):

Primary Outcome Measures:

Relapse-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Treatment-related mortality [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	160
Study Start Date:	June 1996

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

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

National Cancer Institute (NCI)

Investigators

Study Chair:

Teresa Field, MD, PhD

H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000067767, MCC-11281, MCC-IRB-4188, NCI-G00-1759
Study First Received:	June 2, 2000
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00005797 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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
chronic idiopathic 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
myelodysplastic/myeloproliferative disease, 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

Study placed in the following topic categories:

Polycythemia
Chronic Myelomonocytic Leukemia
Cyclosporine
Cyclosporins
Refractory Anemia
Preleukemia
Acute Myelocytic Leukemia
Anemia, Refractory
Hemorrhagic Disorders
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Methotrexate
Thrombocythemia, Hemorrhagic
Etoposide
Myelodysplastic Myeloproliferative Disease

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Myeloproliferative Disorders
Leukemia, Myeloid
Multiple Myeloma
Folic Acid
Leukemia, Myeloid, Accelerated Phase
Chronic Myelogenous Leukemia
Antimetabolites
Leukemia, Lymphoid
Immunologic Factors

Additional relevant MeSH terms:

Anti-Infective Agents
Cyclosporine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cyclosporins
Preleukemia
Pathologic Processes
Hemorrhagic Disorders
Therapeutic Uses
Abortifacient Agents
Methotrexate
Cardiovascular Diseases
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Abortifacient Agents, Nonsteroidal
Multiple Myeloma
Neoplasms
Antimetabolites
Precancerous Conditions
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Paraproteinemias
Cyclophosphamide
Reproductive Control Agents

ClinicalTrials.gov processed this record on July 02, 2009