Clinical trial NCT00382109 (phase 3, status: completed)
Conditions: 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
ICD codes: C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, D89.810, D89.811, D89.813, D89.812
Drugs: thiotepa, cyclophosphamide, tacrolimus, methotrexate, sirolimus
SMILES: CN(C)CCOC(C)(C1=CC=CC=C1)C1=CC=CC=N1, ClCCN(CCCl)P1(=O)NCCCO1, COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O, CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O, CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2
Eligibility criteria:

        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