Clinical trial NCT00105001
Conditions: Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Previously Treated Myelodysplastic Syndrome Refractory Chronic Lymphocytic Leukemia Refractory Plasma Cell Myeloma Waldenstrom Macroglobulinemia Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Lymphoma Childhood Myelodysplastic Syndrome Stage II Contiguous Adult Burkitt Lymphoma Stage II Contiguous Adult Diffuse Large Cell Lymphoma Stage II Contiguous Adult Diffuse Mixed Cell Lymphoma Stage II Contiguous Adult Diffuse Small Cleaved Cell Lymphoma Stage II Adult Contiguous Immunoblastic Lymphoma Stage II Contiguous Adult Lymphoblastic Lymphoma Stage II Grade 1 Contiguous Follicular Lymphoma Stage II Grade 2 Contiguous Follicular Lymphoma Stage II Grade 3 Contiguous Follicular Lymphoma Stage II Contiguous Mantle Cell Lymphoma Stage II Non-Contiguous Adult Burkitt Lymphoma Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma Stage II Non-Contiguous Adult Diffuse Mixed Cell Lymphoma Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma Stage II Adult Non-Contiguous Immunoblastic Lymphoma Stage II Non-Contiguous Adult Lymphoblastic Lymphoma Stage II Grade 1 Non-Contiguous Follicular Lymphoma Stage II Grade 2 Non-Contiguous Follicular Lymphoma Stage II Grade 3 Non-Contiguous Follicular Lymphoma Stage II Non-Contiguous Mantle Cell Lymphoma Stage II Small Lymphocytic Lymphoma Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt 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 Adult Immunoblastic Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Burkitt Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Recurrent Childhood Hodgkin Lymphoma Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Secondary Myelodysplastic Syndrome Stage I Adult Burkitt Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Mixed Cell Lymphoma Stage I Adult Immunoblastic Lymphoma Stage I Adult Lymphoblastic Lymphoma Stage I Childhood Anaplastic Large Cell Lymphoma Stage I Childhood Large Cell Lymphoma Stage I Childhood Lymphoblastic Lymphoma Stage I Childhood Burkitt Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Small Lymphocytic Lymphoma Stage II Childhood Anaplastic Large Cell Lymphoma Stage II Childhood Lymphoblastic Lymphoma Stage II Childhood Burkitt Lymphoma Stage III Adult Burkitt Lymphoma 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 Immunoblastic Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Childhood Anaplastic Large Cell Lymphoma Stage III Childhood Large Cell Lymphoma Stage III Childhood Lymphoblastic Lymphoma Stage III Childhood Burkitt 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 III Marginal Zone Lymphoma Stage III Small Lymphocytic Lymphoma Stage IV Adult Burkitt 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 Immunoblastic Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Childhood Anaplastic Large Cell Lymphoma Stage IV Childhood Large Cell Lymphoma Stage IV Childhood Lymphoblastic Lymphoma Stage IV Childhood Burkitt Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Small Lymphocytic Lymphoma
Sponsor: Fred Hutchinson Cancer Center
Start date: 2004-11-01; Completion date: 2015-05-08
Enrollment: 210 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized phase II trial studies how well giving tacrolimus and mycophenolate mofetil (MMF) with or without sirolimus works in preventing acute graft-versus-host disease (GVHD) in patients undergoing donor stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, 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 system 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 MMF and tacrolimus with or without sirolimus after transplant may stop this from happening.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine which of 3 GVHD prophylaxis regimens results in reduction of acute grades II-IV GVHD to =\< 40%.

SECONDARY OBJECTIVES:

I. Reduce the incidence of non-relapse mortality from infections and GVHD before day 200 to =\< 15%.

II. Reduce the utilization of high-dose corticosteroids compared to protocols 1463, 1641, and 1668.

III. Compare survival and progression-free survival to that achieved under protocols 1463, 1641, and 1668.

OUTLINE:

CONDITIONING: All patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2 and undergo total-body irradiation on day 0.

TRANSPLANTATION: All patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

IMMUNOSUPPRESSION: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive tacrolimus IV or orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

ARM II: Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

ARM III: Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

After completion of study treatment, patients are followed up at 6 months and then every year thereafter.

Arms: arm 1: Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD. arm 2: Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD. arm 3: Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.
Interventions: intervention 1: Fludarabine Phosphate intervention 2: Total-Body Irradiation intervention 3: Peripheral Blood Stem Cell Transplantation intervention 4: Allogeneic Hematopoietic Stem Cell Transplantation intervention 5: Tacrolimus intervention 6: Mycophenolate Mofetil intervention 7: Sirolimus
Intervention descriptions: intervention 1: Given IV intervention 2: Undergo total-body irradiation intervention 3: Undergo allogeneic peripheral blood stem cell transplantation intervention 4: Undergo allogeneic peripheral blood stem cell transplantation intervention 5: Given IV or PO intervention 6: Given PO intervention 7: Given PO

Protocol documents: