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

Completed · Phase 3

Conditions studied: 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, T-cell Childhood Acute Lymphoblastic Leukemia

In brief

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.

Key facts

Study ID

NCT00382109

Run by

Children's Oncology Group

People needed

146

Starts

2007-03-01

Expected to finish

2017-06-30

Last updated by the study team

2019-08-07

Who can join

Age: 1 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

Where it is running

• Phoenix Childrens Hospital — Phoenix, Arizona, United States
• City of Hope Medical Center — Duarte, California, United States
• Children's Hospital and Research Center at Oakland — Oakland, California, United States
• Childrens Hospital of Orange County — Orange, California, United States
• Rady Children's Hospital - San Diego — San Diego, California, United States
• University of California San Francisco Medical Center-Parnassus — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• All Children's Hospital — St. Petersburg, Florida, United States
• Children's Healthcare of Atlanta - Egleston — Atlanta, Georgia, United States
• Childrens Memorial Hospital — Chicago, Illinois, United States
• Indiana University Medical Center — Indianapolis, Indiana, United States
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States
• Kosair Children's Hospital — Louisville, Kentucky, United States
• Children's Hospital-Main Campus — New Orleans, Louisiana, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• C S Mott Children's Hospital — Ann Arbor, Michigan, United States
• Wayne State University — Detroit, Michigan, United States
• The Childrens Mercy Hospital — Kansas City, Missouri, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• Columbia University Medical Center — New York, New York, United States
• University of Rochester — Rochester, New York, United States
• New York Medical College — Valhalla, New York, United States

Full record on ClinicalTrials.gov

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