Donor Bone Marrow Transplant in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00005622

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

158

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy 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 stem cells from a related or unrelated donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow to 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 leukemia, lymphoma, or nonmalignant hematologic disorders.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Multiple Myeloma and Malignant Plasma Cell Neoplasms Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Drug: cyclophosphamide Radiation: TBI	Phase 2

Detailed Description

OBJECTIVES:

Determine the survival of allogeneic bone marrow transplantation using closely matched related and unrelated donors in patients with malignant or nonmalignant hematological disorders.
Determine the incidence and severity of acute and chronic graft versus host disease with this treatment regimen in these patients.
Determine the relapse rates with this treatment regimen in those patients with malignant disorders.
Determine the incidence and severity of infectious complications associated with this treatment regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days -6 and -5, total body radiotherapy on days -3 through 0, and allogeneic bone marrow transplantation on day 0.

Patients with acute lymphocytic leukemia (ALL) receive intrathecal methotrexate at the beginning of the study. If CNS involvement is documented, patients receive a second dose of methotrexate 48 hours later followed by oral leucovorin calcium every 6 hours for 4 doses. Patients with ALL and/or CNS involvement receive intrathecal methotrexate every other week for 12 weeks after transplant.

Patients with prior CNS involvement receive radiotherapy for 2.5 weeks prior to transplant. Patients with ALL receive total body radiotherapy for 5 consecutive days prior to transplant.

Patients are followed once a week for 3 months, and then monthly for 1 year.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 6 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Allogeneic Bone Marrow Transplantation Using Closely Matched Related and Unrelated Donors

Study Start Date :

May 1, 1996

Actual Primary Completion Date :

Sep 1, 2005

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Cy/TBI cyclophosphamide and total body irradiation (TBI)	Drug: cyclophosphamide Cyclophosphamide is administered at a dose of 60 mg/kg on each of two successive days (Days -6 and -5) Radiation: TBI FTBI is performed on day -3 through day 0 The total dose of radiation is 1,320 cGy.

Arm

Intervention/Treatment

Other: Cy/TBI

cyclophosphamide and total body irradiation (TBI)

Drug: cyclophosphamide

Cyclophosphamide is administered at a dose of 60 mg/kg on each of two successive days (Days -6 and -5)

Radiation: TBI

FTBI is performed on day -3 through day 0 The total dose of radiation is 1,320 cGy.

Outcome Measures

Primary Outcome Measures

event free survival (EFS) [five year post transplant]
EFS determined by the Kaplan-Meier product limit method

Secondary Outcome Measures

Incidence of graft versus host disease [five years post transplant]
incidence and severity of acute and chronic GVHD

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of one of the following:
Acute lymphocytic leukemia (ALL):
Complete remission (CR) 1 - high risk defined as overt CNS involvement or poor cytogenetics (additions, deletions, translocations, or multiple abnormalities)
CR2
Induction failures
Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt
Acute myelogenous leukemia (AML):
CR1 - high risk defined as poor cytogenetics (deletions, additions, multiple abnormalities)
CR2
Induction failures
Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt
Chronic myelogenous leukemia (CML):
Chronic phase (CP) 1
Accelerated phase/CP2 - patients in blast phase must undergo treatment and achieve a second chronic phase prior to transplant
Chronic lymphocytic leukemia (CLL):
Relapse - any stage; must have received no more than 3 prior regimens
Multiple myeloma:
At diagnosis - primary refractory
Relapse (no more than 2) - sensitive disease
Plasma cell leukemia
Inability to achieve a complete remission after autologous transplant (no older than 40)
Myelodysplasia - all subtypes
Myeloproliferative disorders - patients with poor response to medical therapy or cytogenetic abnormalities
Severe aplastic anemia (SAA):
Very SAA - at diagnosis
SAA - induction therapy
Donors must be a phenotypic (6 out of 6) match or a one antigen (A or B) mismatch