Allogeneic GM-CSF Vaccine and Lenalidomide in Treating Myeloma Patients With Near Complete Remission

Phase 2

Completed

Conditions: Multiple Myeloma

Interventions: Drug: Lenalidomide
Biological: Allogeneic Myeloma Vaccine
Biological: Prevnar-13

Registration Number: NCT01349569

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Myeloma Vaccine, Prevnar, & Lenalidomide	Allogeneic Myeloma Vaccine	Lenalidomide will be continued on the same dose as was being administered prior to the study. The allogeneic myeloma vaccine and Prevnar-13 vaccine will be given on four days over the course of the study.
Myeloma Vaccine, Prevnar, & Lenalidomide	Prevnar-13	Lenalidomide will be continued on the same dose as was being administered prior to the study. The allogeneic myeloma vaccine and Prevnar-13 vaccine will be given on four days over the course of the study.
Myeloma Vaccine, Prevnar, & Lenalidomide	Lenalidomide	Lenalidomide will be continued on the same dose as was being administered prior to the study. The allogeneic myeloma vaccine and Prevnar-13 vaccine will be given on four days over the course of the study.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.