Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia

Status: Recruiting
Phase: Phase 3
Diagnosis: Pediatric Oncology, Pediatric Leukemia
NCT ID: NCT01190930 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 12-211

 

This partially randomized phase III clinical trial is studying different combinations of risk-adapted chemotherapy regimens and their side effects and comparing how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.

 

Conducting Institutions:
Massachusetts General Hospital

Overall PI:
Alison Friedmann, MD, Massachusetts General Hospital

Site-responsible Investigators:

Contacts:
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

DISEASE CHARACTERISTICS: - Enrolled on COG-AALL08B1 - Newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) - NCI standard-risk (SR) disease - Meets the criteria for one of the following risk groups after induction therapy††: - Low-risk (LR) disease, defined as meeting the following criteria: - Favorable genetics: the presence of simultaneous trisomies of chromosome 4 and 10 (double trisomy; DT) or ETV6/RUNX1 fusion - Day 8 peripheral blood (PB) minimal residual disease (MRD) < 0.01% - Day 29 bone marrow (BM) MRD < 0.01% - No CNS2*, CNS3*, or testicular† leukemia - No steroid pretreatment - No Down syndrome (DS) - No unfavorable genetic characteristics, defined as: - iAMP21 as identified by fluorescence in-situ hybridization (FISH) - MLL rearrangements as identified by cytogenetics, FISH, or molecular studies - Hypodiploidy: Fewer than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone - Induction failure: M3 marrow on Day 29 - Philadelphia chromosome positive (Ph+) ALL - BCR-ABL1 (formerly known as BCR-ABL) fusion transcript determined by FISH or RT-PCR - t(9;22)(q34;q11) determined by cytogenetics - Average-risk disease, defined as meeting one of the following sets of criteria: - Favorable genetics: the presence of DT or ETV6/RUNX1 fusions - Day 8 PB MRD ≥ 0.01% or CNS2* status - Day 29 BM MRD < 0.01% - No CNS3* or testicular† leukemia - No DS OR - Neither favorable nor unfavorable cytogenetics - Day 8 PB MRD < 1% - Day 29 BM MRD < 0.01% - No CNS3* or testicular† leukemia - No DS - Standard-risk with Down syndrome (DS), defined as meeting the following criteria: - No mixed-lineage leukemia (MLL)-rearrangement, hypodiploidy, or Philadelphia chromosome-positive (Ph+) disease - Day 29 BM MRD < 0.01%‡‡ - No CNS3* or testicular† leukemia NOTE: ‡‡DS-ALL patients who have day 29 BM MRD > 0.01% will be eligible for post-induction therapy on the DS stratum of the high-risk trial. NOTE: *CNS2 disease is defined as, in cerebrospinal fluid (CSF), presence of < 5/mm3 WBCs and cytospin positive for blasts, or traumatic lumbar puncture (LP) ≥ 5/mm3 WBCs cytospin positive for blasts, but negative by Steinherz/Bleyer algorithm. CNS3 disease is defined as, in CSF, after traumatic LP presence of ≥ 5/mm3 WBCs and cytospin positive for blasts and/or clinical signs of CNS leukemia. The CNS status must be determined based on a sample obtained before administration of any systemic or intrathecal chemotherapy. NOTE: †Testicular leukemia is defined as unilateral or bilateral testiculomegaly. Biopsy is required if clinical findings are equivocal or suggestive of hydrocele or a non-leukemic blast. NOTE: †† Patients entered on this study who are later found to meet eligibility criteria for the COG-AALL0622 Ph+ ALL study should be immediately be taken off study therapy before day 15 of induction therapy if they are eligible to transfer to COG-AALL06222 or its successor study or otherwise, at the end of induction therapy. - Patients enrolled in AALL0932 who are identified to have iAMP21 will be classified as Very High Risk and will not be eligible to continue on AALL0932 after Induction therapy, but will be eligible to enroll in AALL1131 for post-Induction therapy PATIENT CHARACTERISTICS: - WBC count < 50,000/mm^3 PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No prior cytotoxic chemotherapy for the current diagnosis of ALL or any cancer diagnosed previously - Steroids* and intrathecal cytarabine for the current diagnosis of ALL allowed - Inhalational steroids are not considered as pretreatment NOTE: *If steroids are given for 24 hours in the 2 weeks before diagnosis and a complete blood count (CBC) is obtained within 3 days before the initiation of the steroid, the patient will be assigned to induction based on NCI risk group using the pre-steroid WBC count. If there is no pre-steroid CBC obtained, the patient will be assigned to receive induction therapy on the COG high-risk study. Post-induction risk assignment will be refined by leukemia-specific genetic features and the level of bone marrow minimal residual disease at day 29, except that SR patients in this group will not be eligible for the LR arm. Any amount of steroid pretreatment at any time before 2 weeks before diagnosis will not affect initial induction assignment as long as the patient meets all other eligibility criteria. SR patients in this group may be eligible for the LR arm only if they did not receive steroids within the month before diagnosis.
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