Stage III Multiple Myeloma, Stage II Multiple Myeloma
Conditions
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.
Interventions
BIOLOGICALaflibercept
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (Complete [CR] and Partial Response [PR]) | At baseline and every 4 weeks during study treatment until treatment discontinuation due to disease progression, unacceptable toxicities and/or patient withdrawal. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Time from first treatment day until death, assessed up to 6 months | Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae. |
| Toxicities | up to 6 months | 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. |
| Tissue Expression Patterns of VEGFR Subtypes | At baseline and post-treatment (1 week after 2nd dose and end of study) | 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. |
| Progression-free Survival (PFS) | Time from first treatment day until objective or symptomatic progression, assessed up to 6 months | Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae. |
| Proangiogenic Factors Such as VEGF | At baseline, before every course for 3 months, and then every 3 months during treatment for the first year | 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. |
| Circulating Endothelial Progenitors | At baseline, before every course for 3 months, and then every 3 months during treatment for the first year | 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. |
| The Apoptotic State of Tumor Neovasculature | At baseline and post-treatment (1 week after 2nd dose and end of study) | 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. |
Countries
United States
Participant flow
Recruitment details
A total of 6 patients were enrolled at two institutions between January 2007 and April 2010
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Antiangiogenesis Therapy) 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.
aflibercept: Given IV | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Disease progression during treatment | 5 |
Baseline characteristics
| Characteristic | Treatment (Antiangiogenesis Therapy) |
|---|---|
| Age, Continuous | 59 years |
| Race/Ethnicity, Customized African American | 1 participants |
| Race/Ethnicity, Customized Unknown | 1 participants |
| Race/Ethnicity, Customized White | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
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.
Time frame: At baseline and every 4 weeks during study treatment until treatment discontinuation due to disease progression, unacceptable toxicities and/or patient withdrawal.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Antiangiogenesis Therapy) | Overall Response Rate (Complete [CR] and Partial Response [PR]) | Disease progression | 5 participants |
| Treatment (Antiangiogenesis Therapy) | Overall Response Rate (Complete [CR] and Partial Response [PR]) | Stable disease | 1 participants |
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.
Time frame: At baseline, before every course for 3 months, and then every 3 months during treatment for the first year
Population: data not collected
Secondary
Overall Survival (OS)
Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
Time frame: Time from first treatment day until death, assessed up to 6 months
Population: Overall survival was not assessed by the Kaplan-Meier survival or calculated using the Greenwood's formulae.
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.
Time frame: At baseline, before every course for 3 months, and then every 3 months during treatment for the first year
Population: data not collected
Secondary
Progression-free Survival (PFS)
Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
Time frame: Time from first treatment day until objective or symptomatic progression, assessed up to 6 months
Population: Data not collected
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.
Time frame: At baseline and post-treatment (1 week after 2nd dose and end of study)
Population: data not collected
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.
Time frame: At baseline and post-treatment (1 week after 2nd dose and end of study)
Population: data not collected
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.
Time frame: up to 6 months
Population: Participants with grade 1 and 2 adverse events
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Antiangiogenesis Therapy) | Toxicities | 6 Participants |