Clinical trial NCT00015951: Bevacizumab, Cytarabine, and Mitoxantrone on Treating Patients With Hematologic Cancers
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: University of Maryland Greenebaum Cancer Center
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies such as bevacizumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may be an effective treatment for hematologic cancer.

PURPOSE: Phase II trial to study the effectiveness of bevacizumab combined with cytarabine and mitoxantrone in treating patients who have hematologic cancer.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Judith E. Karp, MD
role: STUDY_CHAIR
References: