Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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

Further Study Information

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.

Eligibility Criteria

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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Gail Roboz

Principal Investigator

U.S.A.
Illinois
	Chicago
	Cancer and Leukemia Group B
		Gail J Roboz	Ph: 646-962-2291
			Email: gar2001@med.cornell.edu

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01420926
Information obtained from ClinicalTrials.gov on February 05, 2013