Aflibercept for Relapsed Multiple Myeloma

NCT00437034 | Terminated Phase 2 Results DMC

• 5 other identifiers: NCI-2009-0018106080086887521P30CA013330N01CM62204
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Progression-free Survival (PFS)

  Time from first treatment day until objective or symptomatic progression, assessed up to 6 months

• Overall Survival (OS)

  Time from first treatment day until death, assessed up to 6 months

• Toxicities

  up to 6 months

• Tissue Expression Patterns of VEGFR Subtypes

  At baseline and post-treatment (1 week after 2nd dose and end of study)

• The Apoptotic State of Tumor Neovasculature

  At baseline and post-treatment (1 week after 2nd dose and end of study)

Study Arms (1)

Treatment (antiangiogenesis therapy)

EXPERIMENTAL

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: aflibercept

Interventions

aflibercept BIOLOGICAL

Given IV

Also known as: vascular endothelial growth factor trap, VEGF Trap, Zaltrap

Treatment (antiangiogenesis therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Medical College of Cornell University

New York, New York, 10065, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Lisa Escobar-Peralta, Program Manager
• Organization: Montefiore Medical Center

lescobar@montefiore.org

718-379-6866

Study Officials

• Ruben Niesvizky-Iszaevich

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: January 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: April 1, 2011
• Last Updated: February 8, 2021
• Results First Posted: July 29, 2015

Record last verified: 2021-01

Locations

US (6)