Aflibercept for Relapsed Multiple Myeloma
Condition: Stage II Multiple Myeloma; Stage III Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: aflibercept
Intervention description: Given IV
Intervention MeSH terms: Aflibercept; Endothelial Growth Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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