Standard Chemotherapy with or Without Nelarabine or Rituximab in Treating Patients with Newly Diagnosed Acute Lymphoblastic Leukemia

RATIONALE: 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. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known which regimen of combination chemotherapy given together with or without monoclonal antibodies is more effective in treating patients with newly diagnosed acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is studying standard chemotherapy to see how well it works when given together with or without rituximab, and with or without nelarabine in treating patients with newly diagnosed acute lymphoblastic leukemia.

Sex

All

Minimum age

25 Years

Maximum age

65 Years

DISEASE CHARACTERISTICS:

* Newly diagnosed, previously untreated acute lymphoblastic leukemia

  * A pre-phase steroid treatment of 5-7 days is required and can be started prior to registration
* Philadelphia chromosome-negative or -positive patients are eligible
* No blast transformation of chronic myeloid leukemia
* No mature B-cell leukemia \[i.e., Burkitt disease t(8,14)(q24 ;q32)\] or variant c-myc translocations \[e.g., t(2;8)(p12;q24), t(8;22)(q24;q11)\]
* Patients who undergo study transplantation must have HLA-compatible sibling or unrelated donor

  * 8/8 molecular match at -A, -B, -C, and -DR (DQ mismatch is permitted)
* Patients meeting ≥ 1 the following criteria are considered high-risk:

  * Over 40 years old
  * WBC ≥ 30 x 10\^9/L (precursor-B) OR ≥ 100 x 10\^9/L (T-lineage)
  * Any 1 or more of the following cytogenetic abnormalities:

    * t(4;11)(q21;q23)/MLL-AF4
    * Low hypodiploidy/near triploidy (30-39 chromosomes/60-78 chromosomes)
    * Complex karyotype (≥ 5 chromosomal abnormalities)
    * Philadelphia chromosome t(9;22) (q34;q11)/BCR-ABL1 (detected by cytogenetic or molecular methods)
  * High-risk minimal-residual disease after completion of part 2 standard induction therapy

PATIENT CHARACTERISTICS:

* No known HIV infection
* Not pregnant or nursing (no nursing during and for 12 months after completion of study therapy)
* Negative pregnancy test
* Fertile patients must use effective contraception during and for up to 12 months after completion of study therapy

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

• DERIVEDMarks DI, Clifton-Hadley L, Copland M, Hussain J, Menne TF, McMillan A, Moorman AV, Morley N, Okasha D, Patel B, Patrick P, Potter MN, Rowntree CJ, Kirkwood AA, Fielding AK. In-vivo T-cell depleted reduced-intensity conditioned allogeneic haematopoietic stem-cell transplantation for patients with acute lymphoblastic leukaemia in first remission: results from the prospective, single-arm evaluation of the UKALL14 trial. Lancet Haematol. 2022 Apr;9(4):e276-e288. doi: 10.1016/S2352-3026(22)00036-9. PMID 35358442
• DERIVEDMarks DI, Kirkwood AA, Rowntree CJ, Aguiar M, Bailey KE, Beaton B, Cahalin P, Castleton AZ, Clifton-Hadley L, Copland M, Goldstone AH, Kelly R, Lawrie E, Lee S, McMillan AK, McMullin MF, Menne TF, Mitchell RJ, Moorman AV, Patel B, Patrick P, Smith P, Taussig D, Yallop D, Alapi KZ, Fielding AK. Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial. Lancet Haematol. 2022 Apr;9(4):e262-e275. doi: 10.1016/S2352-3026(22)00038-2. PMID 35358441
• DERIVEDMitchell RJ, Kirkwood AA, Barretta E, Clifton-Hadley L, Lawrie E, Lee S, Leongamornlert D, Marks DI, McMillan AK, Menne TF, Papaemmanuil E, Patel B, Patrick P, Rowntree CJ, Zareian N, Alapi KZ, Moorman AV, Fielding AK. IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial. Blood Adv. 2021 Sep 14;5(17):3322-3332. doi: 10.1182/bloodadvances.2021004430. PMID 34477813
• DERIVEDPatel B, Kirkwood AA, Dey A, Marks DI, McMillan AK, Menne TF, Micklewright L, Patrick P, Purnell S, Rowntree CJ, Smith P, Fielding AK. Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial. Leukemia. 2017 Jan;31(1):58-64. doi: 10.1038/leu.2016.219. Epub 2016 Aug 2. PMID 27480385