Phase 3
N=146
Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission
B-cell Childhood Acute Lymphoblastic Leukemia · Childhood Acute Lymphoblastic Leukemia in Remission · Graft Versus Host Disease · L1 Childhood Acute Lymphoblastic Leukemia · L2 Childhood Acute Lymphoblastic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT00382109 ↗Enrolled (actual)
146
Serious AEs
9.9%
Results posted
Feb 2017
Primary outcome: Primary: Estimated Percentage of Participants With Event Free Survival — 45; 54 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- thiotepa (Drug); cyclophosphamide (Drug); tacrolimus (Drug); methotrexate (Drug); sirolimus (Drug); total body irradiation (Radiation)
- Age
- Pediatric, Adult · 1+ yrs
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- May 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Estimated Percentage of Participants With Event Free Survival |
45; 54 | — |
| SECONDARY Rate of Relapses |
41; 33 | — |
| SECONDARY Estimated Transplant Related Mortality Percentage |
13; 6 | — |
| SECONDARY Estimated Rate of Acute Graft VS Host Disease (GVHD) |
32; 49 | — |
| SECONDARY Estimated Rate of Overall Chronic Graft VS Host Disease |
22; 27 | — |
| SECONDARY Relative Contribution of Resistance by Acute Lymphoblastic Leukemia (ALL) Blasts to Cytolytic Therapy (e.g., Chemotherapy/Irradiation) as a Cause of Relapse Post-transplantation |
— | — |
| SECONDARY Relative Contribution of ALL Blasts to the Donor Immune Response as a Cause of Relapse Post Transplantation (Correlating Development of aGVHD With Relapse) |
5; 24 | — |
| SECONDARY Relative Contribution of ALL Blasts to the Donor Immune Response as a Cause of Relapse Pre-Transplantation (MRD) |
— | — |
| SECONDARY Chimerism |
— | — |
Summary
This randomized phase III trial is studying tacrolimus, methotrexate, and sirolimus to see how well they work compared to tacrolimus and methotrexate in preventing graft-versus-host disease in young patients who are undergoing donor stem cell transplant for intermediate-risk or high-risk acute lymphoblastic leukemia in second complete remission and high risk acute lymphoblastic leukemia in first remission. Giving chemotherapy, such as thiotepa and cyclophosphamide, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop 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, methotrexate, and sirolimus after the transplant may stop this from happening. It is not yet known whether tacrolimus and methotrexate are more effective with or without sirolimus in preventing graft-versus-host disease.
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed acute lymphoblastic leukemia (ALL) in second complete remission (CR2) (M1 bone marrow, 1% Day 29 or MRD > 0.01% end-Consolidation Block 2) with any available donor, related or unrelated. Patients enrolled on AALL0622 are only eligible if they follow this algorithm.
- Patients with the presence of extreme hypodiploidy ( 0.1% at Day 29).
- Enrolled on an appropriate COG relapsed ALL clinical trial after completing the required study therapy (i.e., minimum 1 re-induction course (4-6 weeks) and 1 round of intensive consolidation chemotherapy (3-6 weeks). Patients with high risk ALL in CR1 are eligible as soon as they have achieved a CR.
- Patients not on a COG relapsed ALL clinical trial are eligible provided they have received ≥ 1 round of re-induction lasting 4-6 weeks and 1 round of intensive consolidation chemotherapy lasting 3-6 weeks
- No B-cell ALL L3 morphology with evidence of myc translocation by molecular or cytogenetic technique
- No Down syndrome
- No evidence of active CNS or other extramedullary disease (i.e., no CNS2)
- Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
- ALT or AST < 5 times upper limit of normal
- Bilirubin < 2.5 mg/dL (unless an increase is attributable to Gilbert's syndrome)
- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min
- FEV\_1 ≥ 60% by pulmonary function tests (PFTs)
- FVC ≥ 60% by PFTs
- DLCO ≥ 60% by PFTs
- For children who are unable to cooperate for PFTs all of the following criteria must be met:
- No evidence of dyspnea at rest
- No exercise intolerance
- No requirement for supplemental oxygen therapy
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No HIV or uncontrolled fungal, bacterial, or viral infection
- Fungal infection acquired during induction therapy allowed provided there is a significant response to antifungal therapy with minimal or no evidence of disease by CT scan
- Other concurrent immunosuppressants allowed
- No prior allogeneic or autologous stem cell transplantation
- No prior or concurrent voriconazole unless prior voriconazole therapy is completed or a different agent is substituted for voriconazole prior to study entry
- No concurrent grapefruit juice during sirolimus administration
Data sourced from ClinicalTrials.gov (NCT00382109). 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.