Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Cancer and Leukemia Group B National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00742625

Purpose

RATIONALE: 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.

PURPOSE: This phase II trial is studying 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.

Condition	Intervention	Phase
Leukemia	Drug: bortezomib Drug: cytarabine Drug: daunorubicin hydrochloride	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine Cytarabine hydrochloride Daunorubicin hydrochloride Daunorubicin Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Dose Escalation and Phase II Study of Bortezomib (IND #58443, NSC # 681239) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Remission induction response rate (complete response [CR] and CR with incomplete platelet recovery [CRp]) [ Designated as safety issue: No ]
Maximum tolerated dose and dose-limiting toxicity of bortezomib when administered in combination with intermediate-dose cytarabine [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Median disease-free survival [ Designated as safety issue: No ]
Median overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	88
Study Start Date:	September 2008
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

To describe the disease-free survival of patients treated with this regimen.
To describe the overall survival of patients treated with this regimen.
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.

Eligibility

Ages Eligible for Study:	60 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
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:
- Steroids administered for adrenal failure, hypersensitivity reactions, or septic shock
- Hormones administered for non-disease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic indications)
No concurrent palliative radiotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00742625

Locations

United States, Delaware
CCOP - Christiana Care Health Services	Recruiting
Newark, Delaware, United States, 19713
Contact: Clinical Trial Office - CCOP - Christiana Care Health Services 302-733-6227
Tunnell Cancer Center at Beebe Medical Center	Recruiting
Lewes, Delaware, United States, 19958
Contact: Clinical Trials Office - Tunnell Cancer Center 302-645-3171
United States, Florida
Florida Hospital Cancer Institute at Florida Hospital Orlando	Recruiting
Orlando, Florida, United States, 32803-1273
Contact: Clinical Trials Office - Florida Hospital Cancer Institute 407-303-5623
United States, Maryland
Union Hospital Cancer Program at Union Hospital	Recruiting
Elkton MD, Maryland, United States, 21921
Contact: Stephen S. Grubbs, MD 302-366-1200
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees	Recruiting
Voorhees, New Jersey, United States, 08043
Contact: Clinical Trials Office - Cancer Institute of New Jersey at Coo 856-325-6757
United States, New York
CCOP - North Shore University Hospital	Recruiting
Manhasset, New York, United States, 11030
Contact: Jonathan E. Kolitz, MD 516-562-8970
Don Monti Comprehensive Cancer Center at North Shore University Hospital	Recruiting
Manhasset, New York, United States, 11030
Contact: Clinical Trials Office - Don Monti Comprehensive Cancer Center 516-734-8900
Long Island Jewish Medical Center	Recruiting
New Hyde Park, New York, United States, 11042
Contact: Jonathan E. Kolitz, MD 516-562-8970
Monter Cancer Center of the North Shore-LIJ Health System	Recruiting
Lake Success, New York, United States, 11042
Contact: Jonathan E. Kolitz, MD 516-562-8970
Roswell Park Cancer Institute	Recruiting
Buffalo, New York, United States, 14263-0001
Contact: Clinical Trials Office - Roswell Park Cancer Institute 877-275-7724
United States, North Carolina
Kinston Medical Specialists	Recruiting
Kinston, North Carolina, United States, 28501
Contact: Peter R. Watson, MD 252-559-2200ext.201
Wake Forest University Comprehensive Cancer Center	Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University Comprehensive 336-713-6771
Wayne Memorial Hospital, Incorporated	Recruiting
Goldsboro, North Carolina, United States, 27534
Contact: James N. Atkins, MD 919-580-0000
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Clinical Trials Office - OSU Comprehensive Cancer Center 614-293-4976 osu@emergingmed.com

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Eyal C. Attar, MD

Massachusetts General Hospital

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000612758, CALGB-10502
Study First Received:	August 27, 2008
Last Updated:	January 10, 2009
ClinicalTrials.gov Identifier:	NCT00742625
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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)
untreated adult acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia without maturation (M1)

adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)

Study placed in the following topic categories:

Leukemia, Monocytic, Acute
Daunorubicin
Bortezomib
Acute myelogenous leukemia
Acute myelomonocytic leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Di Guglielmo's syndrome
Leukemia, Myelomonocytic, Acute

Leukemia
Leukemia, Erythroblastic, Acute
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Congenital Abnormalities
Acute myelocytic leukemia
Acute monoblastic leukemia
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Antibiotics, Antineoplastic
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009