Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Dose Escalation and Phase II Study of Bortezomib (IND #58443) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years
6 other identifiers
interventional
95
1 country
22
Brief Summary
This phase II trial studies the side effects and best dose of bortezomib when given together with daunorubicin and cytarabine and to see how well it works in treating older patients with previously untreated acute myeloid leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2008
Longer than P75 for phase_1
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 27, 2008
CompletedFirst Posted
Study publicly available on registry
August 28, 2008
CompletedStudy Start
First participant enrolled
September 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2012
CompletedResults Posted
Study results publicly available
February 5, 2013
CompletedSeptember 12, 2014
June 1, 2014
1.8 years
August 27, 2008
January 2, 2013
September 4, 2014
Conditions
Outcome Measures
Primary Outcomes (2)
Remission Induction Response
Response was calculated according to Revised International Working Group (IWG) criteria for Acute myeloid leukemia (AML) A response was defined as the portion of participants who achieved a complete response (CR) or CR with incomplete platelet recovery(CRp) during induction. A CR is defined as those with \> 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, \<5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils \> 1000 mL and platelets \>= 100,000 mL). A CRp is defined as a CR except platelets \< 100,000 mL without need for transfusion.
2 months
Participants Experiencing a Dose-limiting Toxicity (DLT) of Bortezomib When Administered in Combination With Intermediate-dose Cytarabine
DLTs were considered only during the first cycle of consolidation therapy and included grade 3 or 4 sensory or autonomic neuropathy, persistent grade 4 thrombocytopenia or neutropenia at day 42 in the absence of AML,any grade 4 or 5 nonhematologic toxicity, and any grade 3 nonhematologic toxicity (excluding neuropathy and toxicities secondary to neutropenia and sepsis) that did not resolve to grade 2 by day 42 unless attributable to persistent or recurrent AML. Grade 4 anorexia (requiring total parenteral nutrition) and grade 4 fatigue (requiring bed rest) were not considered DLTs. Toxicity was graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grading scale is as follows: grade 1: mild; grade 2: moderate; grade 3: Severe; grade 4: Life Threatening; grade 5: Death.
during consolidation cycle 1 (42 days)
Secondary Outcomes (2)
Disease-free Survival
Duration of study (up to 10 years)
Overall Survival
Duration of study (up to 10 years)
Study Arms (1)
Treatment (daunorubicin hydrochloride and bortezomib)
EXPERIMENTALSee Detailed Description
Interventions
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Unequivocally histologically confirmed acute myeloid leukemia (AML)
- At least 20% blasts in the bone marrow based on WHO criteria
- No acute promyelocytic leukemia (M3)
- Antecedent hematologic disorder or myelodysplastic syndromes allowed provided the patient did not receive cytotoxic chemotherapy, including azacitidine and decitabine, for their pre-leukemic disorder
- Concurrent enrollment on CALGB-8461 required
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No ataxia, cranial neuropathy, or peripheral neuropathy \>= grade 2
- LVEF \>= 40% by ECHO or MUGA scan
- No signs or symptoms of congestive heart failure
- DLCO \>= 50% (corrected for hemoglobin)
- No prior therapy for leukemia or pre-leukemic disorders, except for the following:
- emergency leukapheresis;
- emergency treatment for hyperleukocytosis with hydroxyurea;
- cranial radiotherapy for CNS leukostasis (one dose only);
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, 20057, United States
Florida Hospital
Orlando, Florida, 32803, United States
University of Chicago
Chicago, Illinois, 60637, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
University of Missouri - Ellis Fischel
Columbia, Missouri, 65212, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
North Shore University Hospital
Manhasset, New York, 11030, United States
North Shore-LIJ Health System CCOP
Manhasset, New York, 11030, United States
Long Island Jewish Medical Center
New Hyde Park, New York, 11040, United States
North Shore-LIJ Health System/Center for Advanced Medicine
New Hyde Park, New York, 11040, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Kinston Medical Specialists PA
Kinston, North Carolina, 28501, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Related Publications (2)
Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.
PMID: 36184192DERIVEDWalker CJ, Kohlschmidt J, Eisfeld AK, Mrozek K, Liyanarachchi S, Song C, Nicolet D, Blachly JS, Bill M, Papaioannou D, Oakes CC, Giacopelli B, Genutis LK, Maharry SE, Orwick S, Archer KJ, Powell BL, Kolitz JE, Uy GL, Wang ES, Carroll AJ, Stone RM, Byrd JC, de la Chapelle A, Bloomfield CD. Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia. Clin Cancer Res. 2019 Nov 1;25(21):6524-6531. doi: 10.1158/1078-0432.CCR-19-0725. Epub 2019 Aug 2.
PMID: 31375516DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Eyal Attar, MD
- Organization
- Massachusetts General Hospital Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Eyal Attar
Cancer and Leukemia Group B
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 27, 2008
First Posted
August 28, 2008
Study Start
September 1, 2008
Primary Completion
July 1, 2010
Study Completion
December 1, 2012
Last Updated
September 12, 2014
Results First Posted
February 5, 2013
Record last verified: 2014-06