Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer

• Status: Completed
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antilymphocyte Serum; Cyclophosphamide; Etoposide; Etoposide phosphate; Everolimus; Fludarabine; Fludarabine phosphate; Melphalan; Methotrexate; Sirolimus; Tacrolimus; Vidarabine

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of hematological malignancy including any of the following:

• Non-Hodgkin lymphoma (NHL) in any complete remission (CR) or partial response (PR)

• Hodgkin lymphoma in any CR or PR

• Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR

• Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood absolute blast count < 500/µL on the day of initiation of conditioning for patients with non-CR AML or ALL

• Myelodysplastic syndromes (MDS) treated or untreated

• Chronic myelogenous leukemia (CML) in chronic or accelerated phase

• Multiple myeloma in any CR or PR

• Chronic lymphocytic leukemia in CR or PR 2 or greater

• Myelofibrosis and other myeloproliferative disorders

• Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood absolute blast count < 500/µL on the day of initiation

• High-risk disease defined as AML or ALL > CR1, accelerated phase CML, recurrent aggressive lymphoma, or active lymphoproliferative disease at transplant

• Low-risk disease defined as AML or ALL in CR1, chronic phase CML, or low-grade lymphoproliferative disorder with controlled disease at transplant

• Must be planning to receive 1 of the following conditioning regimens at City of Hope:

• Fludarabine phosphate and melphalan for patients with hematological malignancies and contraindications for conventional myeloablative regimens due to age, co-morbidity, or previous transplant

• Fractionated total-body irradiation (FTBI) and etoposide for patients with AML and ALL or CML in accelerated phase

• FTBI and cyclophosphamide for patients with NHL, AML, CML, and MDS

• Suitable unrelated donor available

• HLA-matched or mismatched

• Peripheral blood stem cells available

• No bone marrow or ex vivo-engineered or processed graft (e.g., CD34-positive, T-cell depletion)

• No uncontrolled CNS disease

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 70-100% or ECOG PS 0-2

• Creatinine < 1.3 mg/dL or creatinine clearance ≥ 70 mL/min

• Ejection fraction > 45%

• Direct bilirubin < 3 times upper limit of normal (ULN)

• ALT and AST < 3 times ULN

• Forced vital capacity, FEV1, and DLCO > 45% of predicted

• Able to cooperate with oral medication intake

• No active donor or recipient serology positive for HIV

• No known contraindication to administration of sirolimus, tacrolimus, or anti-thymocyte globulin

• No active hepatitis B or C

• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Concurrent participation in other clinical trials for prevention or treatment of viral, bacterial, or fungal disease allowed provided agents do not interact with agents used in the current study