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A Randomized Phase II Trial of Decitabine-Based Induction Strategies for Patients >/= 60 Years Old With Acute Myeloid Leukemia (AML)


Phase 2
60 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

A Randomized Phase II Trial of Decitabine-Based Induction Strategies for Patients >/= 60 Years Old With Acute Myeloid Leukemia (AML)


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 + 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, 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 complete remission (CR) or
complete remission with incomplete blood count recovery (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.


Inclusion Criteria:



- Unequivocal pathologic diagnosis of AML (>= 20% blasts in the bone marrow based on
WHO criteria) EXCLUDING:

- Acute promyelocytic leukemia t(15;17)(q22;q12); PML-RARA

- Acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-RUNXT1 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 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);
CBFB-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 FLT3 mutation and CBF molecular screening results from CALGB 20202

- Absence of FLT3 mutation (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

- 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

- Must be registered on CALGB-8461 (Cytogenetic Studies in Acute Leukemia)

- No prior treatment for acute myeloid leukemia except:

- Emergency leukapheresis

- Emergency treatment for hyperleukocytosis with hydroxyurea

- Cranial radiotherapy (RT) for CNS leukostasis (one dose only)

- Growth factor/cytokine support

- No other concurrent chemotherapy (except hydroxyurea) and/or radiotherapy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival time

Outcome Description:

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.

Outcome Time Frame:

Time from study entry to the date of death due to any cause, assessed up to 10 years

Safety Issue:

No

Principal Investigator

Gail Roboz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02987

NCT ID:

NCT01420926

Start Date:

November 2011

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
North Shore University HospitalManhasset, New York  11030
Eastern Maine Medical CenterBangor, Maine  04401
Weill Medical College of Cornell UniversityNew York, New York  10021
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Mount Sinai Medical CenterNew York, New York  10029
Munson Medical CenterTraverse City, Michigan  49684
Brigham and Women's HospitalBoston, Massachusetts  02115
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Beebe Medical CenterLewes, Delaware  19958
Mecosta County Medical CenterBig Rapids, Michigan  49307
Mountainview MedicalBerlin, Vermont  05602
Harold Alfond Center for Cancer CareAugusta, Maine  04330
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Cancer Centers of the Carolinas - Grove CommonsGreenville, South Carolina  29605
Cancer Centers of the Carolinas - SenecaSeneca, South Carolina  29672
Cancer Centers of the Carolinas - SpartanburgSpartanburg, South Carolina  29307
Presbyterian HospitalCharlotte, North Carolina  28233-3549
University of North CarolinaChapel Hill, North Carolina  27599
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
University Of VermontBurlington,, Vermont  05403
Florida HospitalOrlando, Florida  32803
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Palo Alto Medical Foundation-Camino DivisionMountain View, California  94040
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Margaret R Pardee Memorial HospitalHendersonville, North Carolina  28791
Kinston Medical Specialists PAKinston, North Carolina  28501
Greenville CCOPGreenville, South Carolina  29615
Greenville Memorial HospitalGreenville, South Carolina  29605
University of Missouri - Ellis FischelColumbia, Missouri  65203
East Carolina UniversityGreenville, North Carolina  27858
Cancer Centers of the Carolinas - FarisGreenville, South Carolina  29605
Cancer Centers of the Carolinas-Greer Medical OncologyGreer, South Carolina  29650
Monter Cancer CenterLake Success, New York  11042
Spectrum Health Reed City HospitalReed City, Michigan  49677
Cancer Care Associates-MercyOklahoma City, Oklahoma  73120
Cancer and Leukemia Group BChicago, Illinois  60606
North Shore-LIJ Health System CCOPManhasset, New York  11030
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Bronson Battle CreekBattle Creek, Michigan  49017
Cancer Care Associates-NormanNorman, Oklahoma  73071