Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: bevacizumab (Drug); cytarabine (Drug); idarubicin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: M.D. Anderson Cancer Center Official(s) and/or principal investigator(s):
Srdan Verstovsek, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center
Summary
RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different
ways to stop cancer cells from dividing so they stop growing or die. Bevacizumab may stop the
growth of cancer by stopping blood flow to the leukemic cells in the bone marrow. Giving
idarubicin and cytarabine with bevacizumab may kill more cancer cells. It is not yet know
whether giving idarubicin together with cytarabine is more effective with or without
bevacizumab in treating acute myeloid leukemia.
PURPOSE: This randomized phase II trial is studying how well giving idarubicin and cytarabine
together with bevacizumab works compared to idarubicin and cytarabine alone in treating
patients with newly diagnosed acute myeloid leukemia.
Clinical Details
Official title: Randomized Phase II Trial of Idarubicin + Ara-C +/- Bevacizumab in Patients Age < 60 With Untreated Acute Myeloid Leukemia
Study design: Treatment, Randomized, Active Control
Primary outcome: Proportion of patients who remain alive in the first complete remission (CR) 1 year from achievement of CR assessed every 3 weeks for 1 year
Secondary outcome: Safety of idarubicin+cytarabine+bevacizumab by AdEERS, CBC and chem. (during remission induction & consolidation every 4-7 days, and during maint. tx prior to bevacizumab dose), monthly for 6-12 mo. then every 3 mo. for 2 yrs after study complet.
Detailed description:
OBJECTIVES:
Primary
- Compare the activity of idarubicin and cytarabine with or without bevacizumab in
patients with newly diagnosed acute myeloid leukemia.
- Compare the proportion of patients who survive and remain in first complete remission
(CR) one year from achieving CR after treatment with these regimens.
Secondary
- Compare the safety of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (<
45 vs 45 to 59), cytogenetics (normal vs - 5/-7 vs other), flt 3 status (normal vs mutated),
and type of acute myeloid leukemia (AML) (de novo vs secondary [arising after cytotoxic
therapy or after an antecedent hematologic disorder, defined as a documented abnormality in
blood count for ≥ 3 months before diagnosis of AML]. Patients who require treatment before
cytogenetics or flt 3 status is known (e. g., patients with WBC > 50,000 OR with organ
dysfunction thought to be due to blast infiltration) are stratified only according to age and
type of AML.
- Induction therapy: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV
continuously over 24 hours on days 1-4.
- Arm II: Patients receive idarubicin and cytarabine as in arm I. Patients also
receive bevacizumab* IV over 30-90 minutes on day 1.
Patients who do not achieve complete remission (CR) after the first induction course may
receive a second induction course approximately 28 days* later. Patients who do not achieve
CR after 2 courses are removed from the study.
NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration
schedule, once every 21 days for 1 year from CR date.
- Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every
28 days in the absence of disease progression or unacceptable toxicity.
- Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
- Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV
continuously over 24 hours on days 1-4.
- Course 3: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously
over 24 hours on days 1-2.
After completion of the 4 post-CR chemotherapy courses, patients in arm I induction therapy
do not receive further therapy. Patients in arm II induction therapy continue to receive
bevacizumab as described above.
After completion of study treatment, patients are followed every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 60-120 patients (30-60 per treatment arm) will be accrued for
this study within 12-30 months.
Eligibility
Minimum age: N/A.
Maximum age: 59 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Newly diagnosed acute myeloid leukemia (AML)
- No acute promyelocytic leukemia
- None of the following cytogenetic abnormalities*:
- t(8;21)
- t(16;16)
- inv(16) NOTE: *Enrollment without cytogenetic information is allowed for
patients who require immediate therapy (e. g. patients with WBC > 50,000/mm3
or organ dysfunction thought to be due to blast infiltration of tissues)
- No history or clinical evidence of primary brain tumors or brain metastasis
PATIENT CHARACTERISTICS:
Age
- Under 60
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- No bleeding diathesis or coagulopathy (unless related to AML)
Hepatic
- Bilirubin ≤ 2. 0 times upper limit of normal (ULN)
- ALT ≤ 2. 5 times ULN
Renal
- Creatinine ≤ 2. 0 times ULN
- No proteinuria OR
- No more than 1 g of protein on 24-hour urine collection
Cardiovascular
- LVEF ≥ 50%
- No uncontrolled hypertension
- No New York Heart Association class II-IV congestive heart failure
- No serious cardiac arrhythmia requiring medication
- No peripheral vascular disease ≥ grade II
- No stroke within the past 6 months
- No arterial thromboembolic event within the past 6 months, including any of the
following:
- Transient ischemic attack
- Cerebrovascular accident
- Myocardial infarction
- Unstable angina
- No other clinically significant cardiovascular disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 3-4 months
after study participation
- No serious or non-healing wound ulcer or bone fracture
- No uncontrolled infection
- No significant traumatic injury within the past 28 days
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies
- No history or clinical evidence of CNS disease (e. g., seizures not controlled with
standard medical therapy)
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior or concurrent transfusions or hematopoietic growth factors for AML allowed
- No concurrent prophylactic hematopoietic colony-stimulating factors
Chemotherapy
- Prior or concurrent hydroxyurea for AML allowed
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- More than 28 days since prior major surgery or open biopsy
- No concurrent major surgery
Other
- No other prior therapy for AML
- No concurrent full-dose anticoagulation therapy
- Concurrent prophylactic anticoagulation (e. g. low-dose warfarin to maintain
patency of permanent indwelling IV catheters) allowed provided INR < 1. 5
- No other concurrent anticancer therapies
- No other concurrent investigational cytotoxic agents
Locations and Contacts
Mayo Clinic Scottsdale, Scottsdale, Arizona 85259-5499, United States
Whittingham Cancer Center at Norwalk Hospital, Norwalk, Connecticut 06856, United States
Mayo Clinic - Jacksonville, Jacksonville, Florida 32224, United States
CCOP - Wichita, Wichita, Kansas 67214-3882, United States
CCOP - Grand Rapids, Grand Rapids, Michigan 49503, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States
Hematology Oncology Associates of Central New York, PC - Northeast Center, East Syracuse, New York 13057-4510, United States
Mount Sinai Medical Center, New York, New York 10029, United States
New York Weill Cornell Cancer Center at Cornell University, New York, New York 10021, United States
CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States
M.D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States
Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: October 2004
Last updated: May 23, 2008
|
