Aflibercept in Treating Patients With Stage II or Stage III Multiple Myeloma That Has Relapsed or Not Responded to Previous Treatment

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00437034
First received: February 15, 2007
Last updated: February 13, 2014
Last verified: January 2012
  Purpose

This phase II trial is studying the side effects and how well aflibercept works in treating patients with stage II or stage III multiple myeloma that has relapsed or not responded to previous treatment. Aflibercept may be able to carry cancer-killing substances directly to multiple myeloma cells. It may also stop the growth of multiple myeloma by blocking blood flow to the cancer.


Condition Intervention Phase
Refractory Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Biological: ziv-aflibercept
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of VEGF Trap (NSC 724770) for the Treatment of Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response rate (complete [CR] and partial response [PR]) [ Time Frame: At baseline and every 4 weeks during study treatment ] [ Designated as safety issue: No ]
    A 95% confidence interval will be estimated via binomial proportions.


Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Time from first treatment day until objective or symptomatic progression, assessed up to 6 months ] [ Designated as safety issue: No ]
    Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.

  • Overall survival (OS) [ Time Frame: Time from first treatment day until death, assesseduUp to 6 months ] [ Designated as safety issue: No ]
    Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.

  • Toxicities [ Time Frame: During treatment and follow up ] [ Designated as safety issue: Yes ]
    Toxicities will be assessed and graded according to Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0 terminology. Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimates.

  • Tissue expression patterns of VEGFR subtypes [ Time Frame: At baseline and post-treatment (1 week after 2nd dose and end of study) ] [ Designated as safety issue: No ]
    The change in the prevalence/expression of these markers between pre-and-post treatment samples will be analyzed by McNemar's test. Ninety-five percent confidence intervals will be calculated to assess the precision of the obtained estimates for all laboratory correlates.

  • The apoptotic state of tumor neovasculature [ Time Frame: At baseline and post-treatment (1 week after 2nd dose and end of study) ] [ Designated as safety issue: No ]
    The change in the prevalence/expression of these markers between pre-and-post treatment samples will be analyzed by McNemar's test. Ninety-five percent confidence intervals will be calculated to assess the precision of the obtained estimates for all laboratory correlates.

  • Proangiogenic factors such as VEGF [ Time Frame: At baseline, before every course for 3 months, and then every 3 months during treatment for the first year ] [ Designated as safety issue: No ]
    The change in the prevalence/expression of these markers between pre-and-post treatment samples will be analyzed by McNemar's test. Ninety-five percent confidence intervals will be calculated to assess the precision of the obtained estimates for all laboratory correlates.

  • Circulating endothelial progenitors [ Time Frame: At baseline, before every course for 3 months, and then every 3 months during treatment for the first year ] [ Designated as safety issue: No ]
    The change in the prevalence/expression of these markers between pre-and-post treatment samples will be analyzed by McNemar's test. Ninety-five percent confidence intervals will be calculated to assess the precision of the obtained estimates for all laboratory correlates.


Enrollment: 50
Study Start Date: January 2007
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (antiangiogenesis therapy)
Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: ziv-aflibercept
Given IV
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES:

I. To evaluate the safety and efficacy of VEGF Trap (aflibercept) in patients with relapsed or refractory, stage II or III multiple myeloma (MM).

II. To perform correlative studies in order to evaluate the angiogenic properties of tissue from patients during the course of treatment with VEGF Trap.

OUTLINE: This is a multicenter study.

Patients receive aflibercept intravenously (IV) over 1 hour on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 60 days and then periodically thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed multiple myeloma

    • Stage II or III disease according to Salmon-Durie staging criteria
  • Relapsed or refractory disease
  • Progressive disease
  • Measurable disease, defined by ≥ 1 of the following criteria:

    • Serum M protein ≥ 1.0 g/dL by serum protein electrophoresis
    • Free light chain measurement > 200 mg/dL
    • Urinary M protein excretion ≥ 200 mg/24 hours
  • Must have received ≥ 2 prior therapies* for multiple myeloma that meet the following criteria:

    • Antimyeloma therapeutic regimen consisting of ≥ 1 complete course of single-agent or combination-agent therapy, or a planned series of treatments (e.g., 3-4 courses of induction therapy followed by a stem cell harvest procedure followed by conditioning high-dose therapy supported by stem cell transplantation)
    • Antimyeloma regimen is discontinued because of the development of resistant disease or severe therapy-related toxicity
    • Individual antimyeloma regimen will be considered to have been discontinued when all agents of the regimen have been permanently stopped
    • A prior regimen will not be considered to have been discontinued for the modification of drug doses, or if less than all the agents of a combination regimen have been discontinued, or if the regimen has been halted temporarily for the development of a plateau phase of myeloma
    • Maintenance therapy will not be considered an additional regimen
    • If new agents are added to an existing regimen, presumably because of tumor resistance, the old regimen will be considered to have ended and a new regimen to have started
  • No evidence of central nervous system (CNS) disease, including primary brain tumor or brain metastasis
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • White blood cell (WBC) ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min
  • No albuminuria only

    • Urine protein: creatinine ratio < 1 OR 24-hour urine protein with an albumin level < 500 mg
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No known history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No significant traumatic injury within the past 28 days
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No clinically significant cardiovascular disease, including any of the following:

    • History of cerebrovascular accident within the past 6 months
    • Uncontrolled hypertension (i.e., blood pressure [BP] > 150/100 mm Hg or systolic BP > 180 mm Hg and diastolic BP < 90 mm Hg on ≥ 2 repeated determinations on separate days within the past 3 months)
    • Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months
    • New York Heart Association class III or IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris within the past 6 months
    • Clinically significant peripheral vascular disease within the past 6 months
    • Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
  • No prothrombin time (PT) or international normalized ratio (INR) > 1.5 (unless patient is on full-dose warfarin)
  • No evidence of bleeding diathesis or coagulopathy
  • No uncontrolled intercurrent illness that would limit compliance with study requirements, including ongoing or active infection
  • No psychiatric illness or social situations that would limit study compliance
  • At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 48 hours since prior minor surgical procedures (e.g., bone marrow aspiration or biopsy, fine-needle aspiration, placement or removal of a central venous access device, or biopsy of a skin lesion)
  • More than 28 days since prior major surgery or open biopsy
  • More than 7 days since prior core biopsy
  • Concurrent full-dose anticoagulants (e.g., warfarin) with PT or INR >1.5 allowed provided the following criteria are met:

    • In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
    • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • No concurrent major surgery
  • No concurrent immunosuppressive agents (including steroids)
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00437034

Locations
United States, New York
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
North Shore University Hospital
Manhasset, New York, United States, 11030
Weill Medical College of Cornell University
New York, New York, United States, 10065
Columbia University Medical Center
New York, New York, United States, 10032
Mount Sinai Medical Center
New York, New York, United States, 10029
Sponsors and Collaborators
Investigators
Principal Investigator: Ruben Niesvizky-Iszaevich Montefiore Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00437034     History of Changes
Other Study ID Numbers: NCI-2009-00181, NCI-2009-00181, NYWCCC-0608008688, CDR0000530040, 0608008688, 7521, P30CA013330, N01CM62204
Study First Received: February 15, 2007
Last Updated: February 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Endothelial Growth Factors
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014