Multiple Myeloma
Conditions
Brief summary
This research is being done to find out if the investigators can improve outcomes for multiple myeloma patients by giving a myeloma vaccine to patients who are already on lenalidomide (Revlimid) and in a near complete remission.
Detailed description
This is a single institution, single arm, Phase II study examining the clinical efficacy of an allogeneic GM-CSF secreting myeloma vaccine in combination with lenalidomide. Fifteen (15) patients enrolled in the study must have two disease measurements (including the last one) consistent with a near complete remission (M-spike negative with persistence of immunofixation) per criteria for response in a 6 month period. Patients will continue on the dose of lenalidomide they were on prior to being enrolled but will need to discontinue steroids for at least 4 weeks. Patients will receive 4 vaccinations on day 14(+/-3 days) of cycles 1, 2, 3 and 6 from enrollment that will include both the myeloma vaccine as well as Prevnar.
Interventions
DRUGLenalidomide
Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle).
BIOLOGICALAllogeneic Myeloma Vaccine
A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.
BIOLOGICALPrevnar-13
Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Sponsors
Celgene Corporation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
* Myeloma eligibility criteria are the following: * sustained near complete remission (nCR) for 4 months defined as no measurable M-spike and a positive immunofixation * early biochemical relapse as manifest by going from a true CR (immunofixation negative) to a nCR (immunofixation positive) at any time * conversion from a nCR to the appearance of a monoclonal spike in the serum not greater than 0.3mg/dL * age 18 years and older * Eastern Cooperative Oncology Group performance scores 0-2 * History of measurable serum or urine M protein or free light chains * Life expectancy greater than 12 months * Corrected serum calcium \< 11 mg/dL, and no evidence of symptomatic hypercalcemia * Serum creatinine\< 2 * Absolute Neutrophil Count \>1000 * Platelet \>100,000 * Total bilirubin less than or equal to 1.5 x Upper limit of normal * Aspartate aminotransferase and Alanine transaminase less than or equal to 3 x Upper limit of normal * Negative pregnancy test if applicable * Ability to comprehend and have signed the informed consent. * Disease free of prior malignancies for \< 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. * All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods. * Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin).
Exclusion criteria
* Disease progression after stopping corticosteroids as defined as the appearance of an M-spike \>0.5g/dL * Patients with a known diagnosis of POEMS syndrome, plasma cell leukemia, non-secretory myeloma and amyloidosis. * HIV disease, active infection requiring treatment with antibiotics, anti-fungal or anti-viral agents within 2 weeks of enrollment would be excluded from the study. * Patients who have participated in any clinical trial, within four weeks prior to registration on this trial, which involved an investigational drug. * History of an active malignancy other than myeloma * Autoimmune disease requiring active treatment. * Known contra-indication to any component of Prevnar 13 including the diphtheria toxoid-containing vaccine. * History of latex allergy * History of an autologous stem cell transplant within the past 12 months or less * History of an allogeneic transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Conversion Rate | Up to 1 year | Number of participants who converted from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | Up to 4 years | Median time for conversion of response from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. as measured by immunofixation converting from positive to negative. |
| Effect on Clonogenic Myeloma Precursors | Baseline, Cycle 3 Day 14, Cycle 6 Day 14, and 1 year | Measures of stem cell population and plasma cell population. |
| Grade 3-4 Toxicity | Up to 1 year | Number of participants who experienced grade 3-4 toxicity as per CTCAE 4.0. |
| Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | Baseline, Cycle 3 Day 14, end of study (up to 1 year) | Immunity is measured by the percentage of CD3+/CSFSE-low/IFN-gamma+ cells. A positive result for a given participant is defined as greater than two standard deviations above that participant's baseline. The data are presented as three groups because the responses were analyzed separately, but all participants were part of the single study arm as represented by the remainder of the record. GVAX-specific immune response and Prevnar-specific immune response was assessed in the same patient by using GVAX and Prevnar-specific co-markers. |
Countries
United States
Participant flow
Pre-assignment details
Two participants were screen failures. One participant withdrew consent prior to starting the study.
Participants by arm
| Arm | Count |
|---|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle).
Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.
Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 4 |
Baseline characteristics
| Characteristic | Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 15 / 16 |
| serious Total, serious adverse events | 1 / 16 |
Outcome results
Primary
Response Conversion Rate
Number of participants who converted from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells.
Time frame: Up to 1 year
Population: Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Response Conversion Rate | 8 Participants |
Secondary
Effect on Clonogenic Myeloma Precursors
Measures of stem cell population and plasma cell population.
Time frame: Baseline, Cycle 3 Day 14, Cycle 6 Day 14, and 1 year
Population: Data was not collected for this outcome measure due to technical difficulties in the assay.
Secondary
Grade 3-4 Toxicity
Number of participants who experienced grade 3-4 toxicity as per CTCAE 4.0.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Grade 3-4 Toxicity | 0 Participants |
Secondary
Time to Response
Median time for conversion of response from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. as measured by immunofixation converting from positive to negative.
Time frame: Up to 4 years
Population: Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Time to Response | 11.7 months |
Secondary
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells
Immunity is measured by the percentage of CD3+/CSFSE-low/IFN-gamma+ cells. A positive result for a given participant is defined as greater than two standard deviations above that participant's baseline. The data are presented as three groups because the responses were analyzed separately, but all participants were part of the single study arm as represented by the remainder of the record. GVAX-specific immune response and Prevnar-specific immune response was assessed in the same patient by using GVAX and Prevnar-specific co-markers.
Time frame: Baseline, Cycle 3 Day 14, end of study (up to 1 year)
Population: Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis. Only 8/15 participants experienced complete response (CR), therefore only 8 participants analyzed in the CR rows and 7 participants analyzed in the progressive disease (PD) rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | Complete Response (CR) patients at Baseline | 1.2 percentage of cells | Standard Deviation 0.4 |
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | CR patients at Cycle 3 Day 14 | 7.3 percentage of cells | Standard Deviation 2.6 |
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | CR patients at end of Study | 6.3 percentage of cells | Standard Deviation 1.4 |
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | Progressive Disease (PD) patients at Baseline | 0.43 percentage of cells | Standard Deviation 0.44 |
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | PD patients at Cycle 3 Day 14 | 1.7 percentage of cells | Standard Deviation 2.9 |
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | PD patients at end of study | 0.4 percentage of cells | Standard Deviation 0 |
| GVAX Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | PD patients at end of study | 0.21 percentage of cells | Standard Deviation 0 |
| GVAX Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | Complete Response (CR) patients at Baseline | 0.36 percentage of cells | Standard Deviation 0.6 |
| GVAX Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | Progressive Disease (PD) patients at Baseline | 0.45 percentage of cells | Standard Deviation 0.7 |
| GVAX Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | PD patients at Cycle 3 Day 14 | 5.7 percentage of cells | Standard Deviation 1.4 |
| GVAX Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | CR patients at Cycle 3 Day 14 | 13.3 percentage of cells | Standard Deviation 3 |
| GVAX Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | CR patients at end of Study | 13.7 percentage of cells | Standard Deviation 5.1 |
| Prevnar Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | CR patients at Cycle 3 Day 14 | 4.54 percentage of cells | Standard Deviation 2.1 |
| Prevnar Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | CR patients at end of Study | 3.6 percentage of cells | Standard Deviation 1.4 |
| Prevnar Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | PD patients at end of study | 1.7 percentage of cells | Standard Deviation 0 |
| Prevnar Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | Progressive Disease (PD) patients at Baseline | 0 percentage of cells | — |
| Prevnar Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | Complete Response (CR) patients at Baseline | 0 percentage of cells | — |
| Prevnar Vaccine | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells | PD patients at Cycle 3 Day 14 | 0 percentage of cells | — |