Phase 2
N=32
Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer
Chronic Myeloproliferative Disorders · Graft Versus Host Disease · Infection · Leukemia · Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT00589563 ↗Enrolled (actual)
32
Serious AEs
29.0%
Results posted
Aug 2014
Primary outcome: Primary: Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100 — 37.3 Percentage of patients developing aGVHD
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- anti-thymocyte globulin (Biological); cyclophosphamide (Drug); etoposide (Drug); fludarabine phosphate (Drug); melphalan (Drug); methotrexate (Drug); sirolimus (Drug); tacrolimus (Drug); allogeneic hematopoietic stem cell transplantation (Procedure); hematopoietic stem cell transplantation (Procedure); nonmyeloablative allogeneic hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure); total-body irradiation (Radiation)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- City of Hope Medical Center
- Primary completion
- Feb 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100 |
37.3 | — |
| PRIMARY Severity of Acute GVHD |
9; 9; 9; 1; 0; 4 | — |
| PRIMARY Cumulative Incidence of Chronic GVHD |
62.5 | — |
| PRIMARY Severity of Chronic GVHD |
4; 4; 17; 7 | — |
| SECONDARY Time to Absolute Neutrophil Count Recovery (Engraftment) |
14.5 | — |
| SECONDARY Time to Platelet Count Recovery (Engraftment) |
14 | — |
| SECONDARY Occurence of Infections Including Cytomegalovirus and Epstein-Barr Virus Reactivation |
16; 9; 3; 4 | — |
| SECONDARY Occurrence of Thrombotic Microangiopathy |
7 | — |
| SECONDARY Occurence of Sinusoidal Obstructive Syndrome (SOS) |
1 | — |
| SECONDARY Non-relapse Mortality at 100 Days Post HSCT |
9.4 | — |
| SECONDARY Non-relapse Mortality at Two Years Post HSCT |
15.6 | — |
| SECONDARY Overall Survival at Two Years Post HSCT |
65.6 | — |
| SECONDARY Event Free Survival at Two Years Post HSCT |
61.3 | — |
| SECONDARY Incidence of Disease Relapse/Progression at 2 Years Post HSCT |
12.5 | — |
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 .
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of hematological malignancy including any of the following:
- Non-Hodgkin lymphoma (NHL) in any complete remission (CR) or partial response (PR)
- Hodgkin lymphoma in any CR or PR
- Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR
- Bone marrow blasts CR1, accelerated phase CML, recurrent aggressive lymphoma, or active lymphoproliferative disease at transplant
- Low-risk disease defined as AML or ALL in CR1, chronic phase CML, or low-grade lymphoproliferative disorder with controlled disease at transplant
- Must be planning to receive 1 of the following conditioning regimens at City of Hope:
- Fludarabine phosphate and melphalan for patients with hematological malignancies and contraindications for conventional myeloablative regimens due to age, co-morbidity, or previous transplant
- Fractionated total-body irradiation (FTBI) and etoposide for patients with AML and ALL or CML in accelerated phase
- FTBI and cyclophosphamide for patients with NHL, AML, CML, and MDS
- Suitable unrelated donor available
- HLA-matched or mismatched
- Peripheral blood stem cells available
- No bone marrow or ex vivo-engineered or processed graft (e.g., CD34-positive, T-cell depletion)
- No uncontrolled CNS disease
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 70-100% or ECOG PS 0-2
- Creatinine 45%
- Direct bilirubin 45% of predicted
- Able to cooperate with oral medication intake
- No active donor or recipient serology positive for HIV
- No known contraindication to administration of sirolimus, tacrolimus, or anti-thymocyte globulin
- No active hepatitis B or C
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Concurrent participation in other clinical trials for prevention or treatment of viral, bacterial, or fungal disease allowed provided agents do not interact with agents used in the current study
Data sourced from ClinicalTrials.gov (NCT00589563). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.