Biomarkers to Classify Young Patients With Acute Lymphoblastic Leukemia (ALL) and Remission Induction Therapy in Young Patients With B-Precursor ALL

NCT ID: NCT01225874

Last Updated: 2016-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 3762 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-12-31

Brief Summary

RATIONALE: Studying samples of blood or bone marrow from patients with cancer in the laboratory may help doctors predict how well patients will respond to treatment. 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) may kill more cancer cells.

PURPOSE: This trial is studying biomarkers to classify young patients with acute lymphoblastic leukemia (ALL) and remission induction therapy in young patients with B-precursor ALL.

Detailed Description

OBJECTIVES:

• To provide the clinical and laboratory data necessary for placing each patient with ALL onto the proper therapeutic trial. (Classification)
• To provide an administrative base to capture classification data for correlative studies in ALL treatment protocols and series of historical protocols. (Classification)
• To provide appropriate induction regimens for patients who may then enter risk specific, post-induction therapeutic trials. (Induction therapy)
• To determine the correlation between event-free survival (EFS) and the following measures of minimal-residual disease (MRD)/early response (ER): 1) the rate of peripheral blast count disappearance and the absolute blast count on day 8 as determined morphologically, by flow cytometry, and using molecular techniques; 2) Marrow morphology on day 8, and; 3) MRD as determined by flow cytometry and molecular techniques on bone marrow and peripheral blood samples on day 29. (Induction therapy)

OUTLINE: This is a multicenter study.

• Classification study: Bone marrow or peripheral blood samples are collected and may be analyzed for B- and T-lineage antigen screening; cytochemical stains; cytogenetics (karyotype); immunophenotype screening for MLL, E2A-PBX1, TEL-AML1; immunophenotype detection of minimal-residual disease (MRD); FCM ploidy (DNA index); trisomies 4 and 10 (FISH); molecular testing for BCR/ABL, MLL rearrangements, E2A-PBX1, and TEL-AML1; molecular detection of MRD - Tγ, Tδ, or IgH; acute lymphoblastic leukemia (ALL) cell bank; special T-ALL reference laboratory studies (role of tumor suppressor genes in T-ALL and drug sensitivity profiles in T-ALL); special study for mature B-ALL [t(18;14)(a24;q32)] by FISH; and hematopathology consultation concerning morphology and cytochemistry. The immunophenotype results are used to assign patients to a treatment protocol, to assign patients to post-induction (day 28) risk group and treatment for patients with B-precursor (non-T, non-B) ALL, and to use as reference laboratory MRD results.
• Induction therapy study: Patients are entered on stratum 3 (three drugs) for NCI consensus standard-risk disease (age < 10 years and WBC < 50,000/mm³) or stratum 4 (four drugs) induction therapy for NCI consensus high-risk disease (age ≥ 10 years and/or WBC ≥ 50,000/mm³ or CNS3 disease or testicular disease).

• Stratum 3: Patients receive oral dexamethasone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; pegaspargase intramuscularly (IM) on day 4, 5, or 6; cytarabine intrathecally (IT) on day 1; and methotrexate IT on day 8 (some patients also receive methotrexate IT on days 15 and 22).
• Stratum 4: Patients receive oral prednisone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; IM SC-PEG E. coli asparaginase IM on days 2, 5, 8, 12, 15, and 19; daunorubicin hydrochloride IV over 15-20 minutes on days 8, 15, and 22; and methotrexate IT on days 1 and 8 (some patients also receive methotrexate IT on days 15 and 22).

Based on day 29 bone marrow results, patients may start consolidation therapy, undergo retesting in a week, or receive 2 additional weeks of therapy. Additional therapy comprises oral prednisone thrice daily for 14 days; vincristine sulfate IV and daunorubicin hydrochloride IV over 15-20 minutes on days 29 and 36; and IM pegaspargase on day 29, 30, or 31. After successful remission induction, patients are assigned to COG-P9904, COG-P9905, or COG-P9906 based on the classification study.

Patients undergo bone marrow aspiration on day 8 to determine the prognostic significance of early remission in the context of this therapy.

After completion of study treatment, patients are followed up every 6 months for 4 years and annually thereafter.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stratum 3

Patients receive oral dexamethasone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; pegaspargase intramuscularly (IM) on day 4, 5, or 6; cytarabine intrathecally (IT) on day 1; and methotrexate IT on day 8 (some patients also receive methotrexate IT on days 15 and 22).

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

Given IT

dexamethasone

Intervention Type: DRUG

Given orally

methotrexate

Intervention Type: DRUG

Given IT

pegaspargase

Intervention Type: DRUG

Given IM

vincristine sulfate

Intervention Type: DRUG

Given IV

Stratum 4

Patients receive oral prednisone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; IM SC-PEG E. coli asparaginase on days 2, 5, 8, 12, 15, and 19; daunorubicin hydrochloride IV over 15-20 minutes on days 8, 15, and 22; and methotrexate IT on days 1 and 8 (some patients also receive methotrexate IT on days 15 and 22).

Group Type: EXPERIMENTAL

SC-PEG E. coli L-asparaginase

Intervention Type: DRUG

Given IM

cytarabine

Intervention Type: DRUG

Given IT

daunorubicin hydrochloride

Intervention Type: DRUG

Given IV

methotrexate

Intervention Type: DRUG

Given IT

prednisone

Intervention Type: DRUG

Given orally

Interventions

SC-PEG E. coli L-asparaginase

Given IM

Intervention Type: DRUG

cytarabine

Given IT

Intervention Type: DRUG

daunorubicin hydrochloride

Given IV

Intervention Type: DRUG

dexamethasone

Given orally

Intervention Type: DRUG

methotrexate

Given IT

Intervention Type: DRUG

pegaspargase

Given IM

Intervention Type: DRUG

prednisone

Given orally

Intervention Type: DRUG

vincristine sulfate

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS:

• See Disease Characteristics

PRIOR CONCURRENT THERAPY:

• Previously untreated, with the following exception:

• Steroid treatment* in the 48-hour period just prior to study entry will be allowed provided that a physical examination and CBC with differential were performed IMMEDIATELY prior to beginning steroids and results of both are known NOTE: *Patients on chronic steroid treatment for another disease are NOT eligible for a COG New ALL protocol.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dale J. Pullen, MD

Role: STUDY_CHAIR

University of Mississippi Cancer Clinic

References

Escherich CS, Chen W, Li Y, Yang W, Nishii R, Li Z, Raetz EA, Devidas M, Wu G, Nichols KE, Inaba H, Pui CH, Jeha S, Camitta BM, Larsen E, Hunger SP, Loh ML, Yang JJ. Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children. Blood. 2024 May 30;143(22):2270-2283. doi: 10.1182/blood.2023023336.

Reference Type: DERIVED

PMID: 38446568 (View on PubMed)

Other Identifiers

U10CA030969

Identifier Type: NIH

Identifier Source: secondary_id

View Link

COG-9900

Identifier Type: OTHER

Identifier Source: secondary_id

POG-9900

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000078618

Identifier Type: OTHER

Identifier Source: secondary_id

9900

Identifier Type: -

Identifier Source: org_study_id