Peripheral Stem Cell Transplant in Treating Patients With High-Risk Leukemia

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00066417

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor, that do not exactly match the patient's blood, 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 peripheral stem cell transplant works in treating patients with high-risk leukemia.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Myelodysplastic/Myeloproliferative Diseases	Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: methylprednisolone Drug: therapeutic allogeneic lymphocytes Drug: thiotepa Procedure: allogeneic bone marrow transplantation Procedure: biological therapy Procedure: bone marrow ablation with stem cell support Procedure: bone marrow transplantation Procedure: chemotherapy Procedure: leukocyte therapy Procedure: non-specific immune-modulator therapy Procedure: peripheral blood lymphocyte therapy Procedure: peripheral blood stem cell transplantation Procedure: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Determine the safety of a preparative regimen comprising total body irradiation, cyclophosphamide, thiotepa, and fludarabine, but without anti-thymocyte globulin, in patients with high-risk leukemia treated with peripheral blood stem cell transplantation from partially matched related donors.
Determine the incidence of graft failure, acute graft-versus-host disease (GVHD), and treatment-related mortality in patients treated with this regimen.
Determine rates of chronic GVHD and relapse in patients treated with this regimen.
Determine disease-free and overall survival in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive a preparative regimen comprising total lymphoid irradiation once daily on days -13 to -11; cyclophosphamide IV over 1 hour on days -8 and -7; thiotepa IV over 4 hours every 12 hours on day -6; fludarabine IV over 30 minutes on days -5 to -1; and total body irradiation once on day -1. Patients also receive cyclosporine IV over 12 hours on days -8 to -1 and methylprednisolone IV twice daily on days -3 and -2. Patients receive CD34-enriched T-cell-depleted allogeneic stem cell infusion on day 0.

Patients with disease progression or uncontrolled infection but without grade II or greater graft-versus-host disease may receive up to 3 donor lymphocyte infusions at least 4 weeks apart until disease regression.

Patients are followed at least weekly until day 100 and then at 6, 12, 18, 24, 36, and 48 months.

PROJECTED ACCRUAL: A total of 20-51 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

51 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study Of T-Cell-Depleted Peripheral Blood Stem Cell Transplantation From Partially Matched Related Donors For Patients With High-Risk Leukemia

Actual Study Completion Date :

Jan 1, 2007

Outcome Measures

Primary Outcome Measures

Incidence of graft failure 100 days post-transplant []
Incidence of acute and chronic graft-vs-host disease100 days post-transplant []
Transplant-related mortality 100 days post-transplant []
Disease-free survival 100 days post-transplant []
Overall survival 100 days post-transplant []

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
High-risk myelodysplastic syndromes (MDS), meeting 1 of the following criteria:
Transformation to acute leukemia defined by at least 15% blasts
Secondary to prior treatment with chemotherapy and/or radiotherapy
Presence of complex cytogenetics (at least 3 karyotypic abnormalities)
Monosomy or deletion of chromosome 7
Acute myeloid leukemia (AML), meeting 1 of the following criteria :
High-risk AML in first remission and meeting 1 of the following criteria:
At least 3 karyotypic abnormalities
Monosomy or deletion of chromosome 5 or 7 = 11q23 chromosomal abnormality
Prior diagnosis of MDS
Received prior radiotherapy or chemotherapy
In second or subsequent remission
Primary induction failure or partial remission
Untested or sensitive relapse
Chronic myelogenous leukemia, meeting 1 of the following criteria:
Blast crisis
Accelerated phase disease that has failed prior treatment with imatinib mesylate, defined as a failure to achieve hematologic response after 3 months of standard dose (600 mg/day) therapy or disease progression on therapy
Myeloproliferative disease
The following diagnoses are eligible:
Agnogenic myeloid metaplasia
Essential thrombocythemia
Polycythemia vera
Must have evidence of transformation to acute leukemia
Acute lymphocytic leukemia (ALL), meeting 1 of the following criteria:
High-risk ALL in first remission defined by 1 of the following:
t(9;22) or 11q23 chromosomal abnormality
Complete response at least 4 weeks after induction therapy OR requiring at least 2 induction regimens
Second or subsequent remission
No relapsed leukemia refractory to appropriate salvage therapy
Availability of an HLA-mismatched family donor
Donor age 75 or under
No better donor alternative (i.e., HLA-matched related or unrelated stem cell donor) is available

PATIENT CHARACTERISTICS:

Age

10 to 50

Performance status

ECOG 0-1

Life expectancy

More than 3 months

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin no greater than 4 mg/dL
Transaminases no greater than 3 times upper limit of normal

Renal

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

Cardiovascular

LVEF at least 40%

Pulmonary

DLCO at least 65% of predicted

Other

Not pregnant
Negative pregnancy test
HIV negative
No other prior malignancy except basal cell or squamous cell skin cancer or a remote history of cancer now considered cured
No major organ dysfunction that would preclude transplantation
No major anticipated illness or organ failure that would preclude transplantation
No severe psychiatric illness or mental deficiency that would preclude giving informed consent or complying with study
No uncontrolled infection