Status:
COMPLETED
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
Lead Sponsor:
Children's Oncology Group
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
B-cell Childhood Acute Lymphoblastic Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Eligibility:
All Genders
1-21 years
Phase:
PHASE3
Brief 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 p...
Detailed Description
PRIMARY OBJECTIVES: I. Compare the post-transplant 2-year event-free survival of pediatric patients with intermediate-risk or high-risk acute lymphoblastic leukemia (ALL) in second complete remission...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- Histologically or cytologically confirmed acute lymphoblastic leukemia (ALL) in second complete remission (CR2) (M1 bone marrow, \< 5% blasts by morphology) meeting the following criteria:
- Intermediate risk relapsed ALL in CR2 (may receive matched sibling transplantation only) meeting 1 of the following criteria:
- B-lineage ALL in CR2 after a late first bone marrow (BM) relapse (≥ 36 months after the initiation of primary chemotherapy) with or without associated extramedullary disease
- B-lineage ALL in CR2 after a very early isolated extramedullary relapse (\<18 months from the initiation of primary chemotherapy)
- High risk relapsed ALL in CR2 (may receive other related donor, unrelated donor, or matched sibling transplantation) meeting 1 of the following criteria:
- In CR2 after an early first BM relapse (\< 36 months from initiation of primary chemotherapy)
- T-lineage ALL in CR2 after a first BM relapse occurring at any time after initiation of primary chemotherapy
- Philadelphia chromosome-positive ALL in CR2 after a first BM relapse occurring at any time after the initiation of primary chemotherapy
- T-lineage ALL in CR2 after a very early isolated extramedullary relapse (\<18 months from the initiation of primary chemotherapy)
- High risk de novo ALL in CR1 (may receive matched sibling, other related/unrelated BM/PBSC or unrelated CB transplantation) meeting 1 of the following criteria:
- Patients with the presence of t(9;22) translocation (Ph+) detected by cytogenetic or PCR analysis at initial diagnosis. For patients on AALL0622, the criteria for transplant are 1) any patient with Ph+ ALL with an available matched sibling donor or 2) any patient with Ph+ ALL that is defined as high risk (MRD \> 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 (\< 44 chromosomes or DNA index of \< 0.81) detected by cytogenetic/ploidy analysis at initial diagnosis.
- Patients with the presence of 11q23 (MLL) rearrangements detected by cytogenetic or PCR analysis at initial diagnosis who are slow early responders (M2/M3 at Day 14 or MRD \> 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
Exclusion
Key Trial Info
Start Date :
March 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 30 2017
Estimated Enrollment :
146 Patients enrolled
Trial Details
Trial ID
NCT00382109
Start Date
March 1 2007
End Date
June 30 2017
Last Update
August 7 2019
Active Locations (50)
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1
Phoenix Childrens Hospital
Phoenix, Arizona, United States, 85016
2
City of Hope Medical Center
Duarte, California, United States, 91010
3
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
4
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874