Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01420926
First received: August 19, 2011
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This phase II trial studies how well giving decitabine with or without bortezomib works in treating older patients with acute myeloid leukemia. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether decitabine with or without bortezomib is an effective treatment for acute myeloid leukemia.


Condition Intervention Phase
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: decitabine
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Decitabine-Based Induction Strategies for Patients ≥ 60 Years Old With Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival (OS) time [ Time Frame: Time from study entry to the date of death due to any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    Methods of Kaplan and Meier will also be used to evaluate survival distributions between the two treatment arms. Median and year-based survival estimates will be calculated along with corresponding 95% confidence intervals. In addition, use of Cox proportional hazards models to evaluate differences in OS between the treatment arms with stratification on age group as well as adjustment for other potential factors of interest.


Secondary Outcome Measures:
  • Complete remission rate (CR and CRi) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Defined as the number of patients who achieve a CR divided by the total number of evaluable patients. Will also calculate corresponding 95% binomial confidence intervals for these estimates. Complete remission rates will also be compared between arms using Mantel-Haenszel chi-square tests stratified on age group.

  • Disease-free survival (DFS) [ Time Frame: Time from documentation of complete remission to the time of relapse and/or death, assessed up to 10 years ] [ Designated as safety issue: No ]
    Logrank statistics and Kaplan-Meier plots will be used to estimate and compare the DFS distributions between the two treatment arms. The methods of Kaplan and Meier will be used to calculate median DFS and corresponding 95% confidence intervals.

  • Progression-free survival [ Time Frame: Time from study entry to the time of documented progression of disease, assessed up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier plots will be used to estimate the survival curves. Stratified log-rank tests will be employed to compare each of these time to event endpoints across treatment regimens.

  • Frequency and severity of adverse events using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns for each of the treatment arms.


Estimated Enrollment: 172
Study Start Date: November 2011
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (decitabine)
Patients receive decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to continuation therapy. Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Experimental: Arm II (decitabine and bortezomib)
Patients receive decitabine IV over 1 hour QD on days 2-11 and bortezomib SC on days 1, 4, 8, and 12. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to continuation therapy. Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Drug: bortezomib
Given SC
Other Names:
  • LDP 341
  • MLN341
  • VELCADE

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine if treatment of older acute myeloid leukemia (AML) patients with decitabine and bortezomib significantly improves the overall survival times of older AML patients compared with decitabine alone.

SECONDARY OBJECTIVES:

I. To determine the rate of complete remission (CR) and CR + incomplete blood count recovery (CRi) for each of the 2 treatment regimens in the proposal.

II. To determine the overall survival, progression-free survival, disease-free survival and for each of the treatment regimens on this study.

III. To determine whether ongoing treatment with these regimens prolongs overall survival even in the absence of complete remission.

IV. To describe the frequency and severity of adverse events, as well as the tolerability of each of these regimens in patients treated on this study.

V. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, molecular genetics, white blood cell (WBC) count, blood and bone marrow blast count, age, performance status and comprehensive geriatric assessment on clinical outcomes.

OUTLINE: This is a multicenter study. Patients are stratified according to age (60-69 years vs >= 70 years). Patients are randomized to 1 of 2 treatment arms.

ARM I:

REMISSION INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour once daily (QD) on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CR with CRi proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II:

REMISSION INDUCTION THERAPY: Patients receive decitabine IV over 1 hour QD on days 2-11 and bortezomib subcutaneously (SC) on days 1, 4, 8, and 12. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to continuation therapy.

CONTINUATION THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then once a year for 6 years.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Unequivocal pathologic diagnosis of AML ( = 20% blasts in the bone marrow based on World Health Organization [WHO] criteria) EXCLUDING:

    • Acute promyelocytic leukemia t(15;17)(q22;q12); promyelocytic leukemia (PML)-retinoic acid receptor, alpha (RARA)
    • Acute myeloid leukemia with t(8;21)(q22;q22); runt-related transcription factor 1 (RUNX1)-runt-related transcription factor 1; translocated to, 1 (RUNXT1) as determined by the Ohio State University (OSU) Molecular Reference Laboratory, per Cancer and Leukemia Group B (CALGB) 20202; however patients who (1) are = 75 years; and/or (2) have an ejection fraction of 40%; and/or (3) have a performance status of 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202
    • Acute myeloid leukemia with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); core-binding factor, beta subunit (CBFB)-myosin, heavy chain 11, smooth muscle (MYH11) as determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are = 75 years; and/or (2) have an ejection fraction of 40%; and/or (3) have a performance status of 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the fms-related tyrosine kinase 3 (FLT3) mutation and core-binding factor (CBF) molecular screening results from CALGB 20202
  • Absence of FLT3 mutation (internal tandem duplication [ITD] or point mutation) determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202
  • No prior treatment for acute myeloid leukemia except:

    • Emergency leukapheresis
    • Emergency treatment for hyperleukocytosis with hydroxyurea
    • Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis (one dose only)
    • Growth factor/cytokine support
  • AML patients with an antecedent hematologic disorder (AHD) or myelodysplastic syndrome (MDS) are eligible for this trial provided that they have not received treatment for their AHD or MDS with cytotoxic chemotherapy (e.g., cytarabine, daunorubicin, etc.), decitabine, or bortezomib; patients may have been previously treated with azacitidine if their last dose was >= 90 days prior to starting CALGB-11002
  • AML patients with therapy-related myeloid neoplasms (t-MN) are eligible if they have not received radiation therapy or chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for > 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420926

  Show 55 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Gail Roboz Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01420926     History of Changes
Other Study ID Numbers: NCI-2011-02987, NCI-2011-02987, CDR0000709218, CALGB 11002, CALGB-11002, U10CA031946, P30CA014236
Study First Received: August 19, 2011
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Decitabine
Bortezomib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014