Aflibercept for Relapsed Multiple Myeloma

Stage III Multiple Myeloma Clinical Trial

Official title:

A Phase 2 Study of Aflibercept for the Treatment of Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00437034
• Other study ID #: NCI-2009-00181
• Secondary ID: NCI-2009-0018106
• Status: Terminated
• Phase: Phase 2
• Start date: January 2007
• Est. completion date: April 2011

Study information

• Verified date: January 2021
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: April 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Exclusion criteria:

• 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

• 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

• No concurrent major surgery

• No concurrent immunosuppressive agents (including steroids)

• No other concurrent investigational agents

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Biological:
• aflibercept
Given IV

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	North Shore University Hospital	Manhasset	New York
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (Complete [CR] and Partial Response [PR])	A 95% confidence interval was intended to be estimated via binomial proportions, but was not computed due to small sample size.; Criteria for Response from EBMT, IBMTR, ABMTR: Complete Response:Complete absence of monoclonal protein by immunofixation for a minimum of 6 weeks; Near Complete Response:Absence of serum paraprotein by standard serum/urine protein electrophoresis without disappearance of monoclonal spike by immunofixation; Partial Response:Sustained decrease in production rate of monoclonal serum protein to 50% or less of pretreatment value; Stable Disease: No significant change from baseline; Progression of Disease:Patients with a > or = 25% rise in production rate, new/increased size of lytic lesions/plasmacytomas/progressive marrow plasmacytosis; Symptomatic Deterioration:Patients with deterioration of health requiring discontinuation of treatment w/out objective evidence of disease progression.	At baseline and every 4 weeks during study treatment until treatment discontinuation due to disease progression, unacceptable toxicities and/or patient withdrawal.
Secondary	Progression-free Survival (PFS)	Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.	Time from first treatment day until objective or symptomatic progression, assessed up to 6 months
Secondary	Overall Survival (OS)	Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.	Time from first treatment day until death, assessed up to 6 months
Secondary	Toxicities	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.	up to 6 months
Secondary	Tissue Expression Patterns of VEGFR Subtypes	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.	At baseline and post-treatment (1 week after 2nd dose and end of study)
Secondary	The Apoptotic State of Tumor Neovasculature	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.	At baseline and post-treatment (1 week after 2nd dose and end of study)
Secondary	Proangiogenic Factors Such as VEGF	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.	At baseline, before every course for 3 months, and then every 3 months during treatment for the first year
Secondary	Circulating Endothelial Progenitors	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.	At baseline, before every course for 3 months, and then every 3 months during treatment for the first year