Recurrent Mantle Cell Lymphoma Clinical Trial
Official title:
Nonmyeloablative Hematopoietic Stem Cell Transplantation for Patients With High-Risk Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression Before and After Transplantation
This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system 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 and mycophenolate mofetil after the transplant may stop this from happening
| Status | Completed |
| Enrollment | 53 |
| Est. completion date | February 2014 |
| Est. primary completion date | March 2011 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A and older |
| Eligibility |
Inclusion Criteria: - Chronic myeloid leukemia (CML) in accelerated phase (AP) - Acute myeloid leukemia (AML) with high-risk cytogenetics [del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q, 21q, 17p, t(6:9), t(9;22), complex karyotypes (>= 3 abnormalities)] in complete remission (CR)1 - AML >= CR2; patients should have < 5% marrow blasts at the time of transplant - High-risk ALL defined as: CR1 with high-risk cytogenetics; t(9;22), t(4;11), or hypodiploid (< 45 chromosomes) for pediatric patients; t(9;22), t(8;14), t(4;11), t(1;19) for adult patients; > 4 wk to achieve CR1; >= CR2 (patients should have < 5% marrow blasts at the time of transplant) - Myelodysplastic syndromes (MDS) (>int-1 per IPSS) after >= 1 prior cycle of induction chemotherapy; should have < 5% marrow blasts at the time of transplant - Multiple myeloma (MM) Stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant - Chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) or Hodgkin's Disease (HD) who are ineligible for autologous HSCT or who have resistant/refractory disease and who may benefit from tandem autologous nonmyeloablative allogeneic transplant - Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active graft-versus-host disease (GvHD) requiring immunosuppressive therapy - DONOR: Related donors who are identical for one HLA haplotype and mismatched at the HLA-A, -B, -C or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or -C allele mismatches Exclusion Criteria: - Cross-match positive with donor - Patients with suitably matched related or unrelated donors - Patients with conventional transplant options (a conventional transplant should be the priority for eligible patients =< 50 yr of age who have a related donor mismatched for a single HLA-A, -B or DRB1 antigen) - Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy - Presence of active, serious infection (e.g., mucormycosis, uncontrolled aspergillosis, tuberculosis) - Karnofsky Performance Status < 60 for adult patients - Lansky-Play Performance Score < 60 for pediatric patients - Left ventricular ejection fraction < 35% - Diffusing capacity of the lung for carbon monoxide (DLCO) < 35% and/or receiving supplemental continuous oxygen - Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL or symptomatic biliary disease - Human immunodeficiency virus (HIV)-positive patients - Women of childbearing potential who are pregnant (beta-HCG+) or breast feeding - Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant - Life expectancy severely limited by diseases other than malignancy - DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the HVG direction - DONOR: Cross-match positive with recipient |
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Fred Hutchinson Cancer Research Center | National Cancer Institute (NCI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Donor engraftment (chimerism) | Defined by the detection of more or greater than 50% donor T-cells (CD3+), as a proportion of the total T-cell population | At day +84 | No |
| Primary | Rate of grades III-IV acute GVHD | At day +200 | No | |
| Primary | Non-relapse-related mortality | At day +200 | No | |
| Secondary | Reconstitution of lymphocytes subsets in peripheral blood | At day +84 | No | |
| Secondary | Change in absolute counts of B-cells (CD19+ ), T-cell subsets (determined by differential expression of CD4, CD8 or CD45 isoforms on CD3+ cells) and NK cells (CD16+/CD56+ ) in peripheral blood | Days -6 and +84 | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
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