A Phase II Study of the Recombinant Human Monoclonal Anti-Vascular Endothelial Growth Factor Antibody (rhuMAB VEGF) Bevacizumab (NSC #704865, IND # 7,921) Administered in Times Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Refractory and Relapsed Acute Myelogenous Leukemias (AMLs)
18 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
A Phase II Study of the Recombinant Human Monoclonal Anti-Vascular Endothelial Growth Factor Antibody (rhuMAB VEGF) Bevacizumab (NSC #704865, IND # 7,921) Administered in Times Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Refractory and Relapsed Acute Myelogenous Leukemias (AMLs)
OBJECTIVES:
- Determine the clinical effectiveness of bevacizumab, cytarabine, and mitoxantrone in
patients with poor-risk hematologic malignancies.
- Determine the toxic effects of this regimen in these patients.
- Determine whether this regimen can induce cell apoptosis in these patients.
- Determine the effects of bevacizumab on coagulation profiles in these patients.
OUTLINE: This is a multicenter study.
Patients receive cytarabine IV continuously over 72 hours on days 1-3, mitoxantrone IV over
30-60 minutes on day 4, and bevacizumab IV over 90 minutes on day 8 in the absence of
disease progression or unacceptable toxicity. Patients achieving partial or complete
remission may receive a second course of therapy beginning approximately 30 days after the
completion of the first course.
Patients are followed until death.
PROJECTED ACCRUAL: A total of 12-45 patients will be accrued for this study within 1-3
years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed poor-risk hematologic malignancy
- Relapsed or refractory acute myelogenous leukemia (AML)
- Primary induction failure
- Myelodysplasia(MDS)-related AML
- Secondary AML
- Relapsed or refractory MDS
- Primary induction failure
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
- Chronic myelogenous leukemia in blast crisis
- Failure of prior primary induction therapy or relapse after achieving complete
remission allowed only if no more than 3 courses of prior induction/reinduction
therapy were received
- No hyperleukocytosis (50,000 or more leukemic blasts/mm3)
- No active CNS leukemia
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
- No disseminated intravascular coagulation
Hepatic:
- AST/ALT no greater than 2 times normal
- Alkaline phosphatase no greater than 2 times normal
- Bilirubin no greater than 1.5 times normal
Renal:
- Creatinine no greater than 1.5 times normal
Cardiovascular:
- LVEF at least 45% by MUGA or echocardiogram
- No myocardial infarction within the past 3 months
- No history of severe coronary artery disease
- No cardiomyopathy
- No New York Heart Association class III or IV heart disease (congestive heart
failure)
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active uncontrolled infection
- No history of cytarabine-related neurotoxicity
- No evidence of graft-versus-host disease
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 1 week since prior hematopoietic growth factors including epoetin alfa,
filgrastim (G-CSF), and sargramostim (GM-CSF)
- At least 1 week since prior interleukin-3 or interleukin-11
- At least 4 weeks since prior autologous stem cell transplantation
- At least 90 days since prior allogeneic stem cell transplantation
- No other concurrent immunotherapy
Chemotherapy:
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy and recovered
- No prior cytarabine administered as a 72-hour continuous infusion followed by
mitoxantrone IV over 30 minutes
- No other concurrent chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- No concurrent radiotherapy
Surgery:
- Not specified
Other:
- At least 2 weeks since prior immunosuppressive therapy
- No other concurrent investigational or commercially available antitumor therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Judith E. Karp, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000068576
NCT ID:
NCT00015951
Start Date:
April 2001
Completion Date:
March 2004
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- recurrent adult acute myeloid leukemia
- relapsing chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- refractory anemia with excess blasts
- refractory anemia with excess blasts in transformation
- chronic myelomonocytic leukemia
- secondary acute myeloid leukemia
- previously treated myelodysplastic syndromes
- childhood myelodysplastic syndromes
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Marlene and Stewart Greenebaum Cancer Center, University of Maryland | Baltimore, Maryland 21201-1595 |
| Blood and Marrow Transplant Group of Georgia | Atlanta, Georgia 30342-1601 |
