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

NCT ID: NCT00066417

Last Updated: 2013-05-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2007-01-31

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.

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.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic/Myeloproliferative Diseases

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cyclophosphamide

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

therapeutic allogeneic lymphocytes

Intervention Type: DRUG

thiotepa

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

biological therapy

Intervention Type: PROCEDURE

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

bone marrow transplantation

Intervention Type: PROCEDURE

chemotherapy

Intervention Type: PROCEDURE

leukocyte therapy

Intervention Type: PROCEDURE

non-specific immune-modulator therapy

Intervention Type: PROCEDURE

peripheral blood lymphocyte therapy

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Principal Investigators

Bipin N. Savani, MD

Role: STUDY_CHAIR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

NIH - Warren Grant Magnuson Clinical Center

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

NHLBI-03-H-0209

Identifier Type: -

Identifier Source: secondary_id

CDR0000315900

Identifier Type: -

Identifier Source: org_study_id

NCT00062725

Identifier Type: -

Identifier Source: nct_alias