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Standard Chemotherapy With or Without Nelarabine or Rituximab in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (UKALL14)

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ClinicalTrials.gov Identifier: NCT01085617
Recruitment Status : Recruiting
First Posted : March 12, 2010
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
University College, London

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.


Condition or disease Intervention/treatment Phase
Leukemia Mucositis Oral Complications Biological: palifermin Biological: rituximab Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: fludarabine phosphate Drug: imatinib mesylate Drug: melphalan Drug: mercaptopurine Drug: methotrexate Drug: nelarabine Drug: pegaspargase Drug: vincristine sulfate Procedure: allogeneic hematopoietic stem cell transplantation Radiation: total-body irradiation Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 811 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised phase III trial of standard treatment +/- rituximab for patients with precursor B-cell ALL or nelarabine for patients with T-cell ALL. A further randomisation investigated two schedules of palifermin administration in patients undergoing myeloablative transplant.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Trial for Adults With Newly Diagnosed Acute Lymphoblastic Leukemia
Actual Study Start Date : December 2010
Actual Primary Completion Date : July 2018
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Active Comparator: B1 - Standard therapy
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
Experimental: B2 - Rituximab
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
Active Comparator: T1 - Standard therapy
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
Experimental: T2 - Nelarabine
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
Active Comparator: P1 - standard palifermin
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
Experimental: P2 - collapsed palifermin
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



Primary Outcome Measures :
  1. Event-free survival [ Time Frame: 3 years ]
    Time from randomisation to relapse or death from any cause


Secondary Outcome Measures :
  1. Anti-asparaginase antibodies in patients treated with monoclonal antibody therapy [ Time Frame: Throughout treatment ]
    Antibody levels in sequential samples during pegylated asparaginase treatment

  2. Overall survival [ Time Frame: 3 years ]
    Time from randomisation to death from any cause

  3. Complete remission (CR) rate [ Time Frame: Throughout treatment ]
    Proportion of patients achieving morphological complete remission

  4. Minimal-residual disease quantification after first phase of induction and post-transplantation [ Time Frame: Throughout treatment ]
    Minimal residual disease measured at central laboratory after phase 1 induction and post transplant

  5. Relapse rate (including bone marrow and CNS relapse) [ Time Frame: 3 years ]
    Proportion of patients experiencing a bone marrow of CNS relapse after entering complete remission

  6. Death in CR [ Time Frame: 3 years ]
    Proportion of patients dying while their ALL is in complete remission

  7. Toxicity related to pegaspargase [ Time Frame: Throughout treatment ]
    Rates of hypersensitivity, changes to Erwinia, or withdrawal of asparaginase treatment

  8. Mucositis score in patients treated with palifermin [ Time Frame: 30 days ]
    OMQD score, number of doses of methotrexate given, acute GVHD rates



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01085617


Locations
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United Kingdom
UCL Cancer Institute Recruiting
London, England, United Kingdom, WC1E 6DD
Contact: Contact Person    44-207-830-2833      
Sponsors and Collaborators
University College, London
Investigators
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Principal Investigator: Adele K. Fielding University College London (UCL) Cancer Institute

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01085617     History of Changes
Other Study ID Numbers: CDR0000667211
UCL-08-0167 ( Other Identifier: UCL )
EU-21009 ( Other Identifier: NK )
2009-012717-22 ( EudraCT Number )
UCL-UKALL14 ( Other Identifier: UCL )
MREC-09-H0711-90 ( Other Identifier: Research Ethics Committee )
NCRI-UCL-08-0167 ( Other Identifier: NK )
CRUK-C27995-A9609 ( Other Grant/Funding Number: Cancer Research UK )
First Posted: March 12, 2010    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University College, London:
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

Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Mucositis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases
Cytarabine
Cyclophosphamide
Melphalan
Rituximab
Methotrexate
Fludarabine
Etoposide
Vincristine
Imatinib Mesylate
Daunorubicin
Fludarabine phosphate
Mercaptopurine
Pegaspargase
Immunosuppressive Agents
Immunologic Factors