Combination Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

NCT00967057 | Completed Phase 3

• 5 other identifiers: CCLG-ALLR3CDR0000642221ISCRTN45724312EUDRACT-2004-000052-16EU-20938
• Study Type: interventional
• Target: 470
• Locations: 2 countries
• Sites: 6

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. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia. PURPOSE: This partially randomized phase III trial is studying how well combination chemotherapy works in treating young patients with relapsed or refractory acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

recurrent childhood acute lymphoblastic leukemia; T-cell childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS) of United Kingdom (UK) patients stratified by risk groups

• Evaluation of whether a minimal residual disease (MRD) level of 10(-4) is a suitable criterion at the end of induction therapy on which to decide whether chemotherapy or stem cell transplantation will be most beneficial to patients with intermediate- ...

Secondary Outcomes (5)

• MRD as a surrogate marker for treatment response and PFS

• Comparison of PFS, MRD level at day 35, and toxicity as response variables in patients randomized to receive induction therapy with mitoxantrone hydrochloride or idarubicin

• PFS of all patients (UK, Dutch, Australian, and New Zealand) stratified by risk groups

• Comparison of PFS and overall survival between patients enrolled in this study and patients enrolled in R2 or I-BFM

• Evaluation of whether pre-stem cell transplantation cytoreduction (FLAD) reduces tumor load and how it affects outcome following transplant

Study Arms (2)

Arm I (induction therapy)

EXPERIMENTAL

Patients receive idarubicin IV over 1 hour on days 1 and 2; oral dexamethasone twice daily on days 1-5 and 15-19; intrathecal (IT) methotrexate on days 1 and 8; vincristine sulfate IV on days 3, 10, 17, and 24; and pegaspargase intramuscularly (IM) on days 3 and 17 or asparaginase IM on days 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, and 25.

Drug: asparaginase; Drug: dexamethasone; Drug: idarubicin; Drug: methotrexate; Drug: pegaspargase; Drug: vincristine sulfate

Arm II (induction therapy)

EXPERIMENTAL

Patients receive mitoxantrone IV over 1 hour on days 1 and 2. Patients also receive dexamethasone, methotrexate, vincristine sulfate, and pegaspargase or asparaginase as in arm I.

Drug: asparaginase; Drug: dexamethasone; Drug: methotrexate; Drug: mitoxantrone hydrochloride; Drug: pegaspargase; Drug: vincristine sulfate

Interventions

asparaginase DRUG

Given intramuscularly

Arm I (induction therapy); Arm II (induction therapy)

dexamethasone DRUG

Given orally

Arm I (induction therapy); Arm II (induction therapy)

idarubicin DRUG

Given IV

Arm I (induction therapy)

methotrexate DRUG

Given intrathecally

Arm I (induction therapy); Arm II (induction therapy)

mitoxantrone hydrochloride DRUG

Given IV

Arm II (induction therapy)

pegaspargase DRUG

Given intramuscularly

Arm I (induction therapy); Arm II (induction therapy)

vincristine sulfate DRUG

Given IV

Arm I (induction therapy); Arm II (induction therapy)

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of acute lymphoblastic leukemia (ALL) meeting 1 of the following criteria: * In first relapse after treatment * Has not yet received chemotherapy or radiotherapy for the first relapse * Primary refractory disease * No mature B-cell ALL * Meets criteria for one of the following risk groups: * Standard-risk disease: non-T-cell or T-cell ALL with late isolated extramedullary relapse * Intermediate-risk disease: non-T-cell ALL with early isolated extramedullary relapse or combined marrow and extramedullary relapse; non-T-cell ALL with late combined marrow and extramedullary relapse or isolated marrow relapse; or T-cell ALL with early isolated extramedullary relapse * High-risk disease: non-T-cell ALL with very early isolated extramedullary relapse, combined marrow and extramedullary relapse, or isolated marrow relapse; non-T-cell ALL with early isolated marrow relapse; T-cell ALL with very early isolated extramedullary relapse, combined marrow and extramedullary relapse, or isolated marrow relapse; T-cell ALL with early combined marrow and extramedullary relapse or isolated marrow relapse; or T-cell ALL with late combined marrow and extramedullary relapse or isolated marrow relapse PATIENT CHARACTERISTICS: * Not specified PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior bone marrow transplant

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

Sponsors & Collaborators

• Children's Cancer and Leukaemia Group: lead

Study Sites (6)

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Birmingham Children's Hospital

Birmingham, England, B4 6NH, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, England, BS2 8BJ, United Kingdom

Location

Great Ormond Street Hospital for Children

London, England, WC1N 3JH, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Related Publications (3)

• Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Revesz T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. doi: 10.1016/S0140-6736(10)62002-8. Epub 2010 Dec 3.

  PMID: 21131038 RESULT

• Eckert C, Parker C, Moorman AV, Irving JA, Kirschner-Schwabe R, Groeneveld-Krentz S, Revesz T, Hoogerbrugge P, Hancock J, Sutton R, Henze G, Chen-Santel C, Attarbaschi A, Bourquin JP, Sramkova L, Zimmermann M, Krishnan S, von Stackelberg A, Saha V. Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials. Eur J Cancer. 2021 Jul;151:175-189. doi: 10.1016/j.ejca.2021.03.034. Epub 2021 May 16.

  PMID: 34010787 DERIVED

• Parker C, Krishnan S, Hamadeh L, Irving JAE, Kuiper RP, Revesz T, Hoogerbrugge P, Hancock J, Sutton R, Moorman AV, Saha V. Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial. Lancet Haematol. 2019 Apr;6(4):e204-e216. doi: 10.1016/S2352-3026(19)30003-1. Epub 2019 Feb 27.

  PMID: 30826273 DERIVED

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Asparaginase; Dexamethasone; Idarubicin; Methotrexate; Mitoxantrone; pegaspargase; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Anthraquinones; Anthrones; Anthracenes; Quinones; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Vaskar Saha, MD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 26, 2009
• First Posted: August 27, 2009
• Study Start: October 1, 2002
• Primary Completion: January 1, 2010
• Study Completion: December 1, 2011
• Last Updated: August 12, 2013

Record last verified: 2011-01

Locations

AU (1); GB (5)