Clinical trial NCT00782379
Conditions: Leukemia Lymphoma Myelodysplastic Syndromes
Keywords: stage III adult diffuse large cell lymphoma stage III adult diffuse mixed cell lymphoma stage III adult diffuse small cleaved cell lymphoma stage III adult Hodgkin lymphoma stage III adult lymphoblastic lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage III mantle cell lymphoma stage IV adult diffuse large cell lymphoma stage IV adult diffuse mixed cell lymphoma stage IV adult diffuse small cleaved cell lymphoma stage IV adult Hodgkin lymphoma stage IV adult lymphoblastic lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage IV mantle cell lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma noncontiguous stage II adult diffuse large cell lymphoma noncontiguous stage II adult diffuse mixed cell lymphoma noncontiguous stage II adult diffuse small cleaved cell lymphoma noncontiguous stage II adult lymphoblastic lymphoma noncontiguous stage II grade 1 follicular lymphoma noncontiguous stage II grade 2 follicular lymphoma noncontiguous stage II grade 3 follicular lymphoma noncontiguous stage II mantle cell lymphoma accelerated phase chronic myelogenous leukemia adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission adult acute myeloid leukemia with 11q23 (MLL) abnormalities adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with t(15;17)(q22;q12) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with t(8;21)(q22;q22) chronic myelomonocytic leukemia chronic phase chronic myelogenous leukemia recurrent adult acute myeloid leukemia refractory chronic lymphocytic leukemia relapsing chronic myelogenous leukemia secondary acute myeloid leukemia stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes prolymphocytic leukemia
Sponsor: Northside Hospital, Inc.
Start date: 2008-10-01; Completion date: 2012-04-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving high-dose cyclophosphamide together with tacrolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy works when given together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil, and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.

Detailed description:
OBJECTIVES:

Primary

* To estimate the incidence of graft rejection and severe graft-versus-host disease after myeloablative HLA-mismatched peripheral blood stem cell transplantation (PBSCT) from first-degree relatives in patients with high-risk hematologic malignancies.

Secondary

* To estimate overall survival, relapse, non-relapse mortality, and event-free survival in these patients.
* To characterize additional hematologic and non-hematologic toxicities of myeloablative haploidentical PBSCT.
* To characterize donor hematopoietic chimerism in peripheral blood stem cells after PBSCT.

OUTLINE:

* Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV over 1-2 hours on days -3 and -2.
* Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo infusion of unmanipulated peripheral blood stem cells on day 0.
* Post-transplant regimen: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days 3 and 4, tacrolimus IV over 24 hours or orally twice daily on days 5-180, and oral mycophenolate mofetil 3 times daily on days 5-34 followed by a taper to day 90. Treatment continues in the absence of disease progression or clinically significant graft-vs-host disease.

After completion of PBSCT, patients are followed periodically for 1 year.

Arms: arm 1: All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.
Interventions: intervention 1: busulfan intervention 2: cyclophosphamide intervention 3: fludarabine phosphate intervention 4: mycophenolate mofetil intervention 5: tacrolimus intervention 6: allogeneic hematopoietic stem cell transplantation intervention 7: peripheral blood stem cell transplantation
Intervention descriptions: intervention 1: 110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4) intervention 2: 14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2). intervention 3: 30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3) intervention 4: 15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD. intervention 5: 0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD. intervention 6: Patients to received unmanipulated PBSCs on Day 0 intervention 7: patients to receive unmanipulated PBSCs on day 0

Protocol documents: