Sirolimus, Tacrolimus and Short Course Methotrexate for Prevention of Acute GVHD in Recipients of Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation
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ClinicalTrials.gov Identifier: NCT00612274 |
Recruitment Status
:
Completed
First Posted
: February 11, 2008
Last Update Posted
: November 30, 2016
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Stem Cell Transplantation | Drug: tacrolimus Drug: Sirolimus Drug: Methotrexate | Early Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 26 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Pilot Study of Sirolimus, Tacrolimus and Short Course Methotrexate for Prevention of Acute Graft Versus Host Disease in Recipients of Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation |
Study Start Date : | October 2007 |
Actual Primary Completion Date : | October 2014 |
Actual Study Completion Date : | October 2014 |

Arm | Intervention/treatment |
---|---|
Experimental: 1
sirolimus, tacrolimus and short course methotrexate
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Drug: tacrolimus
Tacrolimus will be administered at a dose of .02mg/kg/d IVCI beginning day -3 until able to take oral medicines reliably. Blood levels will be maintained at 5-10 ng/ml. The oral dose will be 4 times the IV dose. Tacrolimus will be converted to oral dosing prior to hospital discharge. Tacrolimus will be continued until 4 months post transplant (day +120) unless toxicity, refractory GVHD or the development of disease recurrence mandate discontinuation of the drug.
Other Names:
Drug: Sirolimus
Sirolimus will be administered as a 12 mg oral loading dose on day -3 followed by 4mg daily. Sirolimus levels will be obtained on day +0 and then at least twice weekly to maintain a trough serum level of 3-12 ng/ml. Sirolimus will be continued until 5 months post transplant (day +150) unless toxicity, refractory GVHD or the development of disease recurrence mandate discontinuation of the drug.
Other Name: Rapamune
Drug: Methotrexate
Methotrexate, dose #1 will be administered on day +1 post transplantation, as an IV bolus, provided at least 24 hours have elapsed following infusion of donor stem cells at a dose of 10mg/m2. Dose #2 of Methotrexate will be administered 48 hours later, as IV bolus on day +3 at a dose of 5mg/m2.
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- Safety/Efficacy of a novel regimen of sirolimus, tacrolimus and methotrexate [ Time Frame: Upon completion of study ]

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Ages Eligible for Study: | 16 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients must have an identified 8/10 or 9/10 matched unrelated donor identified following a formal search with confirmatory typing through the national marrow donor program as the best available donor. No matched sibling or fully matched unrelated donor has been identified. HLA typing of donor and recipient will be performed by high resolution molecular typing at HLA A, B, C and DRB1/DQ loci. Patients whose best available donor is matched at 8/10 loci must have at least one of the mismatches at the DQ locus. (no more than one mismatch at HLA A,B,C,DR allowed).
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Candidates for this trial will meet the following criteria:
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Adequate organ function for conditioning type:
For patients receiving ablative conditioning
- Left Ventricular ejection fraction >45%
- DLCO >50%
- Creatinine <1.5
- Hepatic enzymes <3x upper limit of normal.
- KPS >70%
For patients receiving non-ablative conditioning:
- KPS >70%
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Patients with the following diseases will be considered eligible:
- AML in first remission with high risk features (poor risk cytogenetic abnormalities9, persistent elevated blast count on day +15 or recovery marrow after induction therapy).
- AML beyond first remission
- ALL in first remission with high risk features (ph+, t4:11)
- ALL beyond first remission
- High risk Myelodysplasia (RAEB-II, RAEB-I with poor-risk cytogenetics)
- Recurrent Aggressive Non-Hodgkins or Hodgkins lymphoma (indolent histologies excluded) who have failed autologous transplant or have had inadequate response to salvage therapy.
- CML with transformation
- CLL with transformation or Fludarabine failure.
- Severe aplastic anemia with recurrence or failure after immunosuppressive therapy.
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Exclusion Criteria:
- Prior allogeneic transplantation
- Active CNS leukemia.
- Female patients who are pregnant or breast feeding
- Karnofsky performance status <70%.
- Active viral, bacterial or fungal infection.
- Patients seropositive for HIV -1,2; HTLV -1,2 (due to the additional immunodeficiency induced by transplantation and immunosuppressive therapy) Requirement for antifungal prophylaxis with Voriconazole for the first 30 days is prohibited.
- Patients not providing informed consent.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00612274
United States, Connecticut | |
Yale University School of Medicine | |
New Haven, Connecticut, United States, 06520 |
Principal Investigator: | Stuart Seropian, M.D. | Yale University |
Responsible Party: | Yale University |
ClinicalTrials.gov Identifier: | NCT00612274 History of Changes |
Other Study ID Numbers: |
0703002455 |
First Posted: | February 11, 2008 Key Record Dates |
Last Update Posted: | November 30, 2016 |
Last Verified: | November 2016 |
Keywords provided by Yale University:
allogeneic |
Additional relevant MeSH terms:
Methotrexate Tacrolimus Sirolimus Everolimus Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |
Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Calcineurin Inhibitors Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents |