Bevacizumab, Cytarabine, and Mitoxantrone on Treating Patients With Hematologic Cancers

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)

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Leukemia
• Intervention / Treatment: Drug: mitoxantrone hydrochloride; Drug: cytarabine; Biological: bevacizumab

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342-1601
      • Blood and Marrow Transplant Group of Georgia
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21201
      • Marlene and Stewart Greenebaum Cancer Center, University of Maryland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Cancer Institute (NCI); University of Maryland Greenebaum Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): April 1, 2003
• Study Completion (Actual): March 1, 2004

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): October 17, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; previously treated myelodysplastic syndromes; secondary acute myeloid leukemia; childhood myelodysplastic syndromes; recurrent adult acute myeloid leukemia; blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Cytarabine; Mitoxantrone
• Other Study ID Numbers: CDR0000068576; MSGCC-0076; NCI-2490