Bone Marrow Transplant in Treating Patients With Hematologic Cancers

Sponsor

H. Lee Moffitt Cancer Center and Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00005797

Collaborator

National Cancer Institute (NCI) (NIH)

125

Enrollment

Location

Arms

172

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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

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 Design

Study Type:

Interventional

Actual Enrollment :

125 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 1993

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Jul 1, 2007

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Relapse-free survival [5 years post transplant]
Relapse free survival 5 post transplant deteremiend by the Kaplan-Meier product-limit method.

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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