Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

NCT ID: NCT00742625

Last Updated: 2014-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2012-12-31

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.

Detailed Description

PRIMARY OBJECTIVES:

I. To define the remission induction response rate (complete response [CR] and CR with incomplete platelet recovery [CRp]) in older patients with previously untreated acute myeloid leukemia treated with induction therapy comprising bortezomib in combination with daunorubicin hydrochloride and cytarabine.

II. To define the maximum tolerated dose of bortezomib when administered in combination with intermediate-dose cytarabine after induction therapy.

SECONDARY OBJECTIVES:

I. To describe the disease-free survival of patients treated with this regimen. II. To describe the overall survival of patients treated with this regimen. III. To evaluate the treatment-related toxicities in these patients.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Doses of bortezomib are escalated during remission consolidation therapy.

REMISSION INDUCTION THERAPY: Remission induction course 1: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11; daunorubicin hydrochloride IV on days 1-3; and cytarabine IV continuously over 168 hours on days 1-7.

After completion of remission induction course 1, patients undergo bone marrow aspiration and biopsy for evaluation of response. Patients achieving a complete response (CR) or partial response (PR) proceed to remission consolidation therapy. Patients achieving a CR with incomplete platelet recovery (CRp) proceed to remission consolidation therapy after platelet counts recover. Patients with persistent leukemia (>= 20% bone marrow cellularity and >= 5% bone marrow myeloblasts) proceed to remission induction course 2.

REMISSION INDUCTION COURSE 2: Patients receive bortezomib IV over 3-5 seconds on days 1 and 4; daunorubicin hydrochloride IV on days 1 and 2; and cytarabine IV continuously over 120 hours on days 1-5.

After completion of remission induction course 2, patients undergo bone marrow aspiration and biopsy for evaluation of response. Patients achieving a CR or PR proceed to remission consolidation therapy. Patients achieving a CRp proceed to remission consolidation therapy after platelet counts recover. Patients with residual leukemia who do not meet the criteria for PR are removed from the study.

REMISSION CONSOLIDATION THERAPY: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and intermediate-dose cytarabine IV over 3 hours on days 1-5. Patients then undergo bone marrow aspiration and biopsy for evaluation of response. Patients achieving a CR or who demonstrate continuing CR receive a second course of remission consolidation therapy beginning 2-4 weeks after blood counts recover.

After completion of study therapy, patients are followed every 2 months for 2 years, every 3 months for 2 years, and then annually for up to 10 years.

Conditions

Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (daunorubicin hydrochloride and bortezomib)

See Detailed Description

Group Type: EXPERIMENTAL

daunorubicin hydrochloride

Intervention Type: DRUG

Given IV

cytarabine

Intervention Type: DRUG

Given IV

bortezomib

Intervention Type: DRUG

Given IV

Interventions

daunorubicin hydrochloride

Given IV

Intervention Type: DRUG

cytarabine

Given IV

Intervention Type: DRUG

bortezomib

Given IV

Intervention Type: DRUG

Other Intervention Names

Cerubidin; Cerubidine; daunomycin hydrochloride; daunorubicin; RP-13057; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; LDP 341; MLN341; VELCADE

Eligibility Criteria

Inclusion Criteria

• 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);
• growth factor/cytokine support
• No other concurrent chemotherapy, except for the following:

• I) steroids administered for adrenal failure, hypersensitivity reactions, or septic shock;
• II) hormones administered for non-disease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic indications)
• No concurrent palliative radiotherapy

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eyal Attar

Role: PRINCIPAL_INVESTIGATOR

Cancer and Leukemia Group B

Locations

Washington Hospital Center

Washington D.C., District of Columbia, United States

Lombardi Comprehensive Cancer Center at Georgetown University

Washington D.C., District of Columbia, United States

Florida Hospital

Orlando, Florida, United States

University of Chicago

Chicago, Illinois, United States

Eastern Maine Medical Center

Bangor, Maine, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

North Shore University Hospital

Manhasset, New York, United States

North Shore-LIJ Health System CCOP

Manhasset, New York, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

North Shore-LIJ Health System/Center for Advanced Medicine

New Hyde Park, New York, United States

Mount Sinai Medical Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Kinston Medical Specialists PA

Kinston, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36184192 (View on PubMed)

Walker 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.

Reference Type: DERIVED

PMID: 31375516 (View on PubMed)

Other Identifiers

NCI-2009-00443

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000612758

Identifier Type: -

Identifier Source: secondary_id

CALGB 10502

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-10502

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014236

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00443

Identifier Type: -

Identifier Source: org_study_id

NCT01647061

Identifier Type: -

Identifier Source: nct_alias