Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00096148

Collaborator

(none)

120

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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. 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

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Basophilic Leukemia Adult Acute Eosinophilic 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 Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Childhood Acute Basophilic Leukemia Childhood Acute Eosinophilic Leukemia Childhood Acute Erythroleukemia (M6) Childhood Acute Megakaryocytic Leukemia (M7) Childhood Acute Monoblastic Leukemia (M5a) Childhood Acute Monocytic Leukemia (M5b) Childhood Acute Myeloblastic Leukemia With Maturation (M2) Childhood Acute Myeloblastic Leukemia Without Maturation (M1) Childhood Acute Myelomonocytic Leukemia (M4) Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies	Drug: idarubicin Drug: cytarabine Biological: bevacizumab Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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 OBJECTIVES:

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Phase II Trial of Idarubicin + Ara-C +/- Bevacizumab in Patients Age < 60 With Untreated Acute Myeloid Leukemia

Study Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Nov 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (idarubicin, cytarabine) Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously over 24 hours on days 1-4. 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.	Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: cytarabine Given IV Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Other: laboratory biomarker analysis Correlative studies
Experimental: Arm II (idarubicin, cytarabine, bevacizumab) 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.	Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: cytarabine Given IV Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Arm I (idarubicin, cytarabine)

Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously over 24 hours on days 1-4. 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.

Drug: idarubicin

Given IV

Other Names:

4-demethoxydaunorubicin

4-DMDR

DMDR

IDA

Drug: cytarabine

Given IV

Other Names:

ARA-C

arabinofuranosylcytosine

arabinosylcytosine

Cytosar-U

cytosine arabinoside

Other: laboratory biomarker analysis

Correlative studies

Experimental: Arm II (idarubicin, cytarabine, bevacizumab)

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.

Drug: idarubicin

Given IV

Other Names:

4-demethoxydaunorubicin

4-DMDR

DMDR

IDA

Drug: cytarabine

Given IV

Other Names:

ARA-C

arabinofuranosylcytosine

arabinosylcytosine

Cytosar-U

cytosine arabinoside

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

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 [13 months from registration]
Fisher's exact test will be used to compare the proportion of patients alive in CR 13 months from registration date. The test has approximately 89% power to detect an absolute increase of 20% in this proportion, testing at the one-sided 0.15 significance level.

Secondary Outcome Measures

Safety of idarubicin+cytarabine+bevacizumab by AdEERS, CBC and chem. [Up to 2 years after study completion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Newly diagnosed acute myeloid leukemia (AML)
No acute promyelocytic leukemia
None of the following cytogenetic abnormalities*:
t(8;21)
t(16;16)
inv(16)
No history or clinical evidence of primary brain tumors or brain metastasis
Performance status - ECOG 0-2
No bleeding diathesis or coagulopathy (unless related to AML)
Bilirubin ≤ 2.0 times upper limit of normal (ULN)
ALT ≤ 2.5 times ULN
Creatinine ≤ 2.0 times ULN
No proteinuria
No more than 1 g of protein on 24-hour urine collection
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
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 or concurrent transfusions or hematopoietic growth factors for AML allowed
No concurrent prophylactic hematopoietic colony-stimulating factors
Prior or concurrent hydroxyurea for AML allowed
More than 28 days since prior major surgery or open biopsy
No concurrent major surgery
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