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Pilot Study of Donor Th2 Cells Generated In Vitro By Sirolimus Treatment With or Without Oral Sirolimus Versus Oral Sirolimus Alone For Prevention Of Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Hematologic Malignancies
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Related Information Registry Information
Alternate Title
Sirolimus in Preventing Graft-Versus-Host Disease in Patients With Hematologic Malignancies Who Are Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Basic Trial Information
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Protocol IDs
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Phase II
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Supportive care, Treatment
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Active
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18 to 75
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NCI
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NCI-04-C-0055 NCT00077480
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Special Category:
NIH Clinical Center trial, NCI Web site featured trial Objectives Primary - Determine the safety and feasibility of donor Th2 cells generated in vitro by sirolimus treatment with or without oral sirolimus vs oral sirolimus alone for graft-versus-host disease (GVHD) prevention after allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies. (Groups 1 and 3 closed to accrual as of 6/27/05 and 12/15/05, respectively; group 2 also closed to accrual.)
- Determine the GVHD rate in patients treated with these regimens. (Groups 1 and 3 closed to accrual as of 6/27/05 and 12/15/05, respectively; group 2 also closed to accrual; group 5 closed to accrual as of 9/22/08.)
Secondary - Determine the pattern of post-transplantation CD4+ and CD8+ T-cell production of Th1- and Th2-type cytokines in patients treated with these regimens. (Groups 1 and 3 closed to accrual as of 6/27/05 and 12/15/05, respectively; group 2 also closed to accrual; group 5 closed to accrual as of 9/22/08.)
- Determine the kinetics of alloengraftment, incidence of opportunistic infection, and incidence of malignant disease in complete remission in patients treated with these regimens. (Groups 1 and 3 closed to accrual as of 6/27/05 and 12/15/05, respectively; group 2 also closed to accrual; group 5 closed to accrual as of 9/22/08.)
- Determine, preliminarily, whether T cells collected after transplantation have increased reactivity to patient tumor cells relative to donor T cells collected before transplantation.
- Determine the pattern of post-transplantation CD14+ monocyte production of inflammatory cytokines interleukin-1-alpha and tumor necrosis factor alpha in patients treated with these regimens. (Groups 1 and 3 closed to accrual as of 6/27/05 and 12/15/05, respectively; group 2 also closed to accrual; group 5 closed to accrual as of 9/22/08.)
Entry Criteria Disease Characteristics:
- Histological diagnosis of 1 of the following hematologic malignancies, myelodysplasia, or myeloproliferative disorders:
- Acute leukemia must be in hematologic remission (less than 5% of blood or marrow blasts)
- Must have a first-degree relative donor matched at 6/6 HLA antigens (A, B, and DR)
- No active CNS involvement by malignancy
Prior/Concurrent Therapy:
Biologic therapy - See Disease Characteristics
Chemotherapy - See Disease Characteristics
Endocrine therapy - No concurrent steroids as antiemetics during chemotherapy
- No concurrent steroids during transplantation
Surgery - See Disease Characteristics
Other - At least 2 weeks since prior therapy and recovered
Patient Characteristics:
Age Performance status Life expectancy Hematopoietic Hepatic - ALT and AST no greater than 2.5 times upper limit of normal*
- Bilirubin less than 2.5 mg/dL*
[Note: *Values above these levels may be accepted, at the discretion of the principal investigator or study chairman, if the elevations are due to liver involvement] Renal - Creatinine no greater than 1.5 mg/dL
- Creatinine clearance at least 50 mL/min
Cardiovascular - LVEF greater than 45% by 2-dimensional ECHO or MUGA
Pulmonary - DLCO greater than 50% of expected
Other - Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 1 year after study participation
- HIV negative
- No active infection that is not responding to antimicrobial therapy
- No psychiatric illness that would preclude study compliance or informed consent
Expected Enrollment 190Approximately 190 patients will be accrued for this study. Outcomes Primary Outcome(s)Safety and feasibility Graft-versus-host disease rate
Secondary Outcome(s)Pattern of post-transplantation CD4+ and CD8+ T-cell production of Th1- and Th2-type cytokines Kinetics of alloengraftment Incidence of opportunistic infection Incidence of malignant disease in complete remission Reactivity of T cells collected after transplantation Pattern of post-transplantation CD14+ monocyte production of inflammatory cytokines, interleukin-1-alpha, and tumor necrosis factor alpha
Outline This is a pilot study. Patients are stratified according to age (18 to 45 vs 46 to 75). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed weekly for 6 weeks post-transplantation, at 3 months, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Trial Contact Information
Trial Lead Organizations NCI - Center for Cancer Research | | | Daniel Fowler, MD, Protocol chair | | | | Trial Sites
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U.S.A. |
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Maryland |
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Bethesda |
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| | | | | | | | NCI - Center for Cancer Research |
| | Clinical Trials Office - NCI - Center for Cancer Research | |
| | Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office |
| | Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office | |
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New Jersey |
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Hackensack |
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| | | Hackensack University Medical Center Cancer Center |
| | Clinical Trials Office - Hackensack University Medical Center Cancer Center | |
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Related Information Featured trial article
Registry Information | | Official Title | | Pilot Study Of Sirolimus (Rapamycin) Generated Donor Th2 Cells And In Vivo Sirolimus For GVHD Prevention After Allogeneic HSCT For Hematologic Malignancy | | Trial Start Date | | 2003-12-30 | | Registered in ClinicalTrials.gov | | NCT00077480 | | Date Submitted to PDQ | | 2003-12-30 | | Information Last Verified | | 2007-11-26 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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