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Bone Marrow Transplant

Sirolimus, Cyclosporine, and Mycophenolate Mofetil In Preventing GVHD for Undergoing Donor Peripheral Blood Stem Cell Transplant (FHCRC-2206)
A Phase II Study to Assess Immunosuppression with Sirolimus Combined with Cyclosporine (CSP) and Mycophenolate mofetil (MMF) for Prevention of Acute GVHD after Non-myeloablative HLA Class I or II Mismatched Donor Hematopoietic Cell Transplantation. A Multi-Center Trial
Status Conditions Phase Study ID
Recruiting Hematologic Malignancies Phase II FHCRC-2206
NCT01251575
Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also 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 total-body irradiation together with sirolimus, cyclosporine, and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving sirolimus together with cyclosporine and mycophenolate mofetil works in preventing graft-vs-host disease in patients with hematologic malignancies undergoing donor peripheral blood stem cell transplant.


Investigator
Brenda Sandmaier, MD
Location    
Seattle Cancer Care Alliance 800-804-8824  
Eligibility Criteria (must meet the following to participate in this study)

 

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages > 50 years with hematologic malignancies treatable by related or unrelated HCT
  • Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who through pre-existing medical conditions or prior therapy are considered to be at high risk for regimen related toxicity associated with a high dose transplant (> 40% risk of TRM); this criterion can include patients with a HCT-CI score of >= 1; transplants should be approved for these inclusion criteria by both the participating institutions' patient review committees such as the Patient Care Conference (PCC) at the FHCRC and by the principal investigators at the collaborating centers; patients =< 50 years of age who have received previous high-dose transplantation do not require patient review committee approvals; all children < 12 years must be discussed with the FHCRC PI (Brenda Sandmaier, MD 206 667 4961) prior to registration
  • Ages =< 50 years of age with chronic lymphocytic leukemia (CLL) (these patients do not require patient review committee approvals)
  • Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who refuse a high-dose HCT; transplants must be approved for these inclusion criteria by both the participating institutions' patient review committee such as PCC at the FHCRC and by the principal investigators at the collaborating centers
  • Aggressive non-Hodgkin lymphomas (NHL) and Other histologies such as Diffuse large B cell NHL: not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT
  • Mantle Cell NHL: may be treated in first CR; (diagnostic LP required pre-transplant)
  • Low grade NHL: with < 6 month duration of CR between courses of conventional therapy
  • CLL: must have either 1) failed to meet NCI Working Group criteria for complete or partial response after therapy with a regimen containing FLU (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-CY-Rituximab (FCR) combination chemotherapy at any time point; or 3) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR
  • Hodgkin Lymphoma: must have received and failed frontline therapy
  • Multiple Myeloma: must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted
  • Acute Myeloid Leukemia (AML): must have < 5% marrow blasts at the time of transplant
  • Acute Lymphocytic Leukemia (ALL): must have < 5% marrow blasts at the time of transplant
  • Chronic Myeloid Leukemia (CML): patients will be accepted if they are beyond CP1 and if they have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant
  • Myelodysplasia(MDS)/Myeloproliferative Syndrome (MPS): Patients must have < 5% marrow blasts at time of transplant
  • Waldenstrom's Macroglobulinemia: must have failed 2 courses of therapy
  • Patients with related or unrelated donors for whom the best available donor is: a) Mismatched at antigen level for any single class I locus (HLA-A, -B, -C) ± an additional class I mismatch at the allele level OR mismatched at the allele level for any 2 class I loci (if typed at the molecular level) OR mismatched at the antigen or allele level for any single class II locus (HLA-DRB1 or - DQB1); b) there is a likelihood of rapid disease progression while HLA typing and results of a preliminary search and the donor pool suggests that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched donor will not be found; c) there is no HLA-A, -B or -C one locus allelic mismatched donor available
  • DONOR: Related or unrelated volunteer donors who are mismatched with the recipient within one of the following limitations: a) mismatch for one HLA class I antigen with or without an additional mismatch for one HLA-class I allele, but matched for HLA-DRB1 and HLA-DQ, OR
  • DONOR: b) mismatched for two HLA class I alleles, but matched for HLA-DRB1 and HLA-DQ, OR
  • DONOR: c) mismatched for one HLA-DRB1 antigen or allele with or without an additional mismatch for one HLA-DQ, but matched for HLA-class I alleles
  • DONOR: HLA-matching must be based on results of high resolution typing at HLA-A, -B, -C, -DRB1, and -DQB
  • DONOR: Two mismatches at a single HLA- locus is not allowed
  • DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the donor should be excluded if any of the flow cytometric B and T cell cytotoxic cross match assays are positive
  • DONOR: Only G-CSF mobilized PBSC only will be permitted as a HSC source on this protocol
Exclusions (conditions that would prevent participation in this study)

Exclusion Criteria:

  • Patients who are homozygous at the mismatched MHC class I locus or II locus
  • Patients for whom the best available donor is mismatched at both HLA class I and class II
  • A positive cross-match exists between the donor and recipient
  • Patients with rapidly progressive intermediate or high grade NHL
  • Patients with a diagnosis of CMML
  • Patients with RAEB who have not received myelosuppressive chemotherapy i.e. induction chemotherapy
  • Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, MDS, ALL or CML
  • CNS involvement with disease refractory to intrathecal chemotherapy
  • Fertile men or women unwilling to use contraceptives during and for up to 12 months following treatment
  • Female patients who are pregnant or breast-feeding
  • HIV positive patients
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Patients with active bacterial or fungal infections unresponsive to medical therapy
  • Cardiac ejection fraction < 35%; ejection fraction is required if the patient is > 50 years of age, or history of cardiac disease or anthracycline exposure
  • Corrected DLCO < 40%, TLC < 40%, FEV1 < 40% and/or receiving supplementary continuous oxygen
  • The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules
  • Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
  • Patients with poorly controlled hypertension on multiple antihypertensives
  • Karnofsky scores < 60 or Lansky Score < 50
  • All patients receiving antifungal therapy voriconazole, posaconazole, or fluconazole must have sirolimus reduced according to the Standard Practice Antifungal Therapy Guidelines
  • The addition of cytotoxic agents for "cytoreduction" with the exception of tyrosine kinase inhibitors (such as imatinib), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning
  • DONOR: Donor (or centers) who will exclusively donate marrow
  • DONORS: who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC
Last Updated
November 29, 2012
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
Disclaimer: We update this information regularly. However, what you read today may not be completely up to date.

Please remember:
  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.