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

NCT01085617 | Completed DMC

• 8 other identifiers: CDR0000667211UCL-08-0167EU-210092009-012717-22UCL-UKALL14MREC-09-H0711-90NCRI-UCL-08-0167CRUK-C27995-A9609
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Leukemia; Mucositis; Oral Complications

Keywords

oral complications; mucositis; untreated adult acute lymphoblastic leukemia; B-cell adult acute lymphoblastic leukemia; T-cell adult acute lymphoblastic leukemia; Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  Time from randomisation to relapse or death from any cause

  3 years

Secondary Outcomes (8)

• Anti-asparaginase antibodies in patients treated with monoclonal antibody therapy

  Throughout treatment

• Overall survival

  3 years

• Complete remission (CR) rate

  Throughout treatment

• Minimal-residual disease quantification after first phase of induction and post-transplantation

  Throughout treatment

• Relapse rate (including bone marrow and CNS relapse)

  3 years

Study Arms (6)

B1 - Standard therapy

ACTIVE COMPARATOR

Standard chemotherapy for precursor B-cell ALL

Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: fludarabine phosphate; Drug: imatinib mesylate; Drug: melphalan; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: vincristine sulfate

B2 - Rituximab

EXPERIMENTAL

Standard chemotherapy for precursor B-cell ALL plus weekly rituximab infusions during phase 1 induction

Biological: rituximab; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: fludarabine phosphate; Drug: imatinib mesylate; Drug: melphalan; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: vincristine sulfate

T1 - Standard therapy

ACTIVE COMPARATOR

Standard chemotherapy for T-cell ALL

Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: fludarabine phosphate; Drug: melphalan; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: vincristine sulfate

T2 - Nelarabine

EXPERIMENTAL

Standard chemotherapy for T-cell ALL plus an additional course of treatment with nelarabine following phase 2 induction

Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: fludarabine phosphate; Drug: melphalan; Drug: mercaptopurine; Drug: methotrexate; Drug: nelarabine; Drug: pegaspargase; Drug: vincristine sulfate

P1 - standard palifermin

ACTIVE COMPARATOR

6 doses of palifermin before/after myeloablative stem cell transplant (randomisation closed due to lack of clinical relevance in 2016)

Biological: palifermin; Procedure: allogeneic hematopoietic stem cell transplantation; Radiation: total-body irradiation

P2 - collapsed palifermin

EXPERIMENTAL

1 x large dose of palifermin before myeloablative stem cell transplant and 3 low doses after transplant (randomisation closed due to lack of clinical relevance in 2016)

Biological: palifermin; Procedure: allogeneic hematopoietic stem cell transplantation; Radiation: total-body irradiation

Interventions

palifermin BIOLOGICAL

P1 - standard palifermin; P2 - collapsed palifermin

rituximab BIOLOGICAL

B2 - Rituximab

cyclophosphamide DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

cytarabine DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

daunorubicin hydrochloride DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

etoposide DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

fludarabine phosphate DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

imatinib mesylate DRUG

B1 - Standard therapy; B2 - Rituximab

melphalan DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

mercaptopurine DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

methotrexate DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

nelarabine DRUG

T2 - Nelarabine

pegaspargase DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

vincristine sulfate DRUG

B1 - Standard therapy; B2 - Rituximab; T1 - Standard therapy; T2 - Nelarabine

allogeneic hematopoietic stem cell transplantation PROCEDURE

P1 - standard palifermin; P2 - collapsed palifermin

total-body irradiation RADIATION

P1 - standard palifermin; P2 - collapsed palifermin

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University College, London: lead

Related Publications (4)

• Marks 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 DERIVED

• Marks 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 DERIVED

• Mitchell 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 DERIVED

• Patel 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 DERIVED

MeSH Terms

Conditions

Leukemia; Mucositis

Interventions

Fibroblast Growth Factor 7; Rituximab; Cyclophosphamide; Cytarabine; Daunorubicin; Etoposide; fludarabine phosphate; Imatinib Mesylate; Melphalan; Mercaptopurine; Methotrexate; nelarabine; pegaspargase; Vincristine; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Piperazines; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Sulfhydryl Compounds; Sulfur Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Adele K. Fielding

  University of York

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: March 12, 2010
• Study Start: December 1, 2010
• Primary Completion: February 24, 2025
• Study Completion: February 24, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03