Clinical trial NCT00437034: Aflibercept for Relapsed Multiple Myeloma
Official title: A Phase 2 Study of Aflibercept for the Treatment of Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stage II Multiple Myeloma
Stage III Multiple Myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-02-19
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

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

Primary outcomes:
measure: Overall Response Rate (Complete [CR] and Partial Response [PR])
timeFrame: At baseline and every 4 weeks during study treatment until treatment discontinuation due to disease progression, unacceptable toxicities and/or patient withdrawal.
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Time from first treatment day until objective or symptomatic progression, assessed up to 6 months
measure: Overall Survival (OS)
timeFrame: Time from first treatment day until death, assessed up to 6 months
measure: Toxicities
timeFrame: up to 6 months
measure: Tissue Expression Patterns of VEGFR Subtypes
timeFrame: At baseline and post-treatment (1 week after 2nd dose and end of study)
measure: The Apoptotic State of Tumor Neovasculature
timeFrame: At baseline and post-treatment (1 week after 2nd dose and end of study)
measure: Proangiogenic Factors Such as VEGF
timeFrame: At baseline, before every course for 3 months, and then every 3 months during treatment for the first year
measure: Circulating Endothelial Progenitors
timeFrame: At baseline, before every course for 3 months, and then every 3 months during treatment for the first year
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Ruben Niesvizky-Iszaevich
role: PRINCIPAL_INVESTIGATOR
References: