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A Phase 2 Study of VEGF Trap (NSC 724770) for the Treatment of Relapsed or Refractory Multiple Myeloma

Phase 2
18 Years
Not Enrolling
Refractory Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

Thank you

Trial Information

A Phase 2 Study of VEGF Trap (NSC 724770) for the Treatment of Relapsed or Refractory Multiple Myeloma


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

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

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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate (complete [CR] and partial response [PR])

Outcome Description:

A 95% confidence interval will be estimated via binomial proportions.

Outcome Time Frame:

At baseline and every 4 weeks during study treatment

Safety Issue:


Principal Investigator

Ruben Niesvizky-Iszaevich

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2007

Completion Date:

Related Keywords:

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



Albert Einstein College of MedicineBronx, New York  10461
North Shore University HospitalManhasset, New York  11030
Weill Medical College of Cornell UniversityNew York, New York  10021
Mount Sinai Medical CenterNew York, New York  10029
Montefiore Medical CenterBronx, New York  10467-2490
Columbia University Medical CenterNew York, New York  10032