Trials / Completed
CompletedNCT00589563
Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer
A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin, as Graft-versus-Host Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
- Status
- Completed
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 32 (actual)
- Sponsor
- City of Hope Medical Center · Academic / Other
- Sex
- All
- Age
- 2 Years
- Healthy volunteers
- Not accepted
Summary
RATIONALE: Giving chemotherapy 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 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, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .
Detailed description
OBJECTIVES: Primary * To determine the incidence and severity of acute- and chronic-graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor hematopoietic peripheral blood transplantation in patients with hematologic malignancies scheduled to receive immunosuppressive combination of sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis. * To determine the safety of this combination in the first six months post-transplant. Secondary * To determine the time-to-engraftment, non-relapse mortality rate, overall and disease-free survival, incidence of disease relapse, and incidence of opportunistic infections with this GVHD prophylaxis. OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate and melphalan vs fractionated total-body irradiation \[FTBI\] and etoposide vs FTBI and cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk). * Conditioning regimen: Patients receive 1 of 3 standard conditioning regimens beginning on day -9 or -8 and continuing to day -1 or 0. * Peripheral blood stem cell transplantation: Patients receive HLA-matched or mismatched unrelated donor peripheral blood stem cells on day 0. * Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously beginning on day -3 and then orally when tolerated, oral sirolimus on days -3 and -2, anti-thymocyte globulin IV over 4-8 hours on days -3 to 0, and methotrexate\* IV on days 1, 3, and 6. Tacrolimus and sirolimus continue for 3-6 months (with taper). NOTE: \*Only patients with high-risk HLA mismatch receive treatment with methotrexate. After completion of study therapy, patients are followed periodically for up to 2 years.
Conditions
- Chronic Myeloproliferative Disorders
- Graft Versus Host Disease
- Infection
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- Precancerous Condition
- Secondary Myelofibrosis
- Small Intestine Cancer
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | anti-thymocyte globulin | 0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.5 mg/kg on day -1 or day 0 from stem cell transplant |
| DRUG | cyclophosphamide | 60mg/kg on days -5 and -4 from stem cell transplant |
| DRUG | etoposide | 60mg/kg on day -4 from stem cell transplant |
| DRUG | fludarabine phosphate | Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant |
| DRUG | melphalan | Melphalan 140 mg/m2 on day -4 from stem cell transplant |
| DRUG | methotrexate | For high risk HLA-mismatch transplant only: 5 mg/m2 on days +1, +3 and +6 from stem cell transplant |
| DRUG | sirolimus | Adults: 12 mg loading dose on day -3 from stem cell transplant followed by 4 mg orally single morning daily dose. Pediatric Patients \<40kg: 3 mg/m2 orally on day -3 from stem cell transplant followed by 1 mg/m2 orally single morning daily dose |
| DRUG | tacrolimus | 0.02 mg/kd/d CIV beginning on day -3 from stem cell transplant |
| PROCEDURE | allogeneic hematopoietic stem cell transplantation | The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight |
| PROCEDURE | hematopoietic stem cell transplantation | The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight |
| PROCEDURE | nonmyeloablative allogeneic hematopoietic stem cell transplantation | Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant, Melphalan 140 mg/m2 on day -4 from stem cell transplant |
| PROCEDURE | peripheral blood stem cell transplantation | The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight |
| RADIATION | total-body irradiation | 1320 cGy in 11 fractions from day -8 to day -5 or day -9 to day -6 prior to stem cell transplant |
Timeline
- Start date
- 2007-05-01
- Primary completion
- 2012-02-01
- Completion
- 2012-02-01
- First posted
- 2008-01-09
- Last updated
- 2014-09-10
- Results posted
- 2014-08-12
Locations
2 sites across 1 country: United States
Source: ClinicalTrials.gov record NCT00589563. Inclusion in this directory is not an endorsement.