Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia
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| ClinicalTrials.gov Identifier: NCT01420926 |
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Recruitment Status :
Active, not recruiting
First Posted : August 22, 2011
Results First Posted : October 24, 2016
Last Update Posted : September 28, 2021
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This randomized 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,by stopping them from dividing, or by stopping them from spreading. 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 works better when given with or without bortezomib in treating acute myeloid leukemia.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Therapy-Related Acute Myeloid Leukemia | Drug: Bortezomib Drug: Decitabine Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Quality-of-Life Assessment Other: Questionnaire Administration | Phase 2 |
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| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 165 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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) |
| Actual Study Start Date : | November 16, 2011 |
| Actual Primary Completion Date : | June 5, 2015 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial acute myeloid leukemia with mutated CEBPA
Cytogenetically normal acute myeloid leukemia
Core binding factor acute myeloid leukemia
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A (decitabine)
REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 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 not achieving CR CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 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:
Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies |
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Experimental: Arm B (decitabine and bortezomib)
REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 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: Bortezomib
Given SC
Other Names:
Drug: Decitabine Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies |
Primary Outcome Measures :
- Overall Survival (OS) Time [ Time Frame: Time from study entry to death assessed up to 10 years ]Overall survival (OS) was defined as the time from study entry to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Secondary Outcome Measures :
- Complete Remission Rate (CR and CRi) [ Time Frame: Duration of study up to 10 years ]Defined as the number of patients who achieve a CR or CRi divided by the total number of evaluable patients. A Complete remission (CR) requires: <5% marrow blast, > 200 nucleated cells, no blasts with auer rods, no extramedullary disease, ANC >1,000/mm^3 and platelets > 100,000/mm^3. A CR with incomplete blood count recovery (CRi) is defined as CR with exception of ANC < 1,000/mm^3 or platelets < 100,000/mm^3.
- Disease-free Survival (DFS) [ Time Frame: Time from study entry to relapse and/or death (up to 10 years) ]Disease free survival (DFS) was defined as the time from CR to relapse or death. Relapse free and surviving patients were censored at the date of last follow-up. The median DFS with 95% CI was estimated using the Kaplan Meier method. Relapse is defined as the reappearance of blood blasts or >= 5% marrow blasts after achieving a CR or CRi.
- Progression-free Survival [ Time Frame: Time from study entry to progression and/or death (up to 10 years) ]Progression free survival (PFS) was defined as the time from study entry to progression or death. Progression free and surviving patients were censored at the date of last follow-up. The median DFS with 95% CI was estimated using the Kaplan Meier method.
- Adverse Events [ Time Frame: Duration of treatment ]Adverse Events: Incidence of adverse events, assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events were collected every cycle during treatment and up to one month after treatment. Adverse events were summarized using summary statistics and frequency tables for each separate cohort. Per protocol, analysis was descriptive in nature. In this section, the number of patients that reported a grade 4 or higher event are summarized. A complete listing of Adverse Events is provided in the Adverse Events section below.
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| Ages Eligible for Study: | 60 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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); PML-RARA
- Acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-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 core-binding factor (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
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No prior treatment for AML 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 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
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): NCT01420926
Locations
Show 53 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Gail J Roboz | Alliance for Clinical Trials in Oncology |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01420926 |
| Other Study ID Numbers: |
NCI-2011-02987 NCI-2011-02987 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000709218 CALGB-11002 ( Other Identifier: Alliance for Clinical Trials in Oncology ) CALGB-11002 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA031946 ( U.S. NIH Grant/Contract ) |
| First Posted: | August 22, 2011 Key Record Dates |
| Results First Posted: | October 24, 2016 |
| Last Update Posted: | September 28, 2021 |
| Last Verified: | August 2021 |
Additional relevant MeSH terms:
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases |
Bortezomib Decitabine Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors |