Description:
This study seeks to determine whether addition of an allogeneic myeloma vaccine can augment
clinical responses to lenalidomide in patients with near complete remission (nCR), or
complete remission (CR) leading to a significant improvement in progression-free
survival.This main objective of this study is to compare the 2-year progression free survival
of patients with multiple myeloma in CR or nCR, treated with lenalidomide plus an allogeneic
myeloma vaccine in combination with lenalidomide (with or without Prevnar vaccine) or versus
placebo in combination with lenalidomide (control arm).
Title
- Brief Title: Allogeneic Myeloma GM-CSF Vaccine With Lenalidomide in Multiple Myeloma Patients in Complete or Near Complete Remission
- Official Title: A Randomized, Double-blind, Placebo-Controlled Phase II Trial of an Allogeneic Myeloma GM-CSF Vaccine With Lenalidomide in Multiple Myeloma Patients in Complete or Near Complete Remission
Clinical Trial IDs
- ORG STUDY ID:
J16118
- SECONDARY ID:
IRB00112179
- NCT ID:
NCT03376477
Conditions
Interventions
Drug | Synonyms | Arms |
---|
GM-CSF vaccine | GVAX | Lenalidomide plus GM-CSF Vaccine |
Lenalidomide | Revlimid | Lenalidomide Only |
Prevnar13 | pneumococcal vaccine | Lenalidomide plus GM-CSF Vaccine plus Prevnar13 |
Purpose
This study seeks to determine whether addition of an allogeneic myeloma vaccine can augment
clinical responses to lenalidomide in patients with near complete remission (nCR), or
complete remission (CR) leading to a significant improvement in progression-free
survival.This main objective of this study is to compare the 2-year progression free survival
of patients with multiple myeloma in CR or nCR, treated with lenalidomide plus an allogeneic
myeloma vaccine in combination with lenalidomide (with or without Prevnar vaccine) or versus
placebo in combination with lenalidomide (control arm).
Detailed Description
This is a single institution, three- arm, randomized controlled, Phase II study examining the
clinical efficacy of an allogeneic GM-CSF secreting myeloma vaccine in combination with
lenalidomide (with or without Prevnar) compared to lenalidomide and placebo (control arm).
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), or complete remission (M-spike negative, negative immunofixation, and <5%
clonal plasma cells on bone marrow) per criteria for response in a 3 month period. All
patients must be minimal residual disease (MRD) positive by NGS sequencing at enrollment.
Prior to enrollment, patients will have been treated with a lenalidomide containing regimen
for a minimum of 6 cycles. All patients will continue on a standard dose of lenalidomide as a
single agent until progression, or treatment limiting toxicity, following enrollment.
Patients will be randomized to receive either an allogeneic myeloma vaccine and Prevnar
vaccine in combination with lenalidomide, or allogeneic myeloma vaccine without Prevnar
vaccine in combination with lenalidomide, or lenalidomide in combination with placebo.
Patients will receive allogeneic myeloma vaccine or placebo injections on day 14 (+/-3 days)
of cycles 1, 2, 3 and 6 from enrollment, and then annually thereafter for up to 3 years. If
assigned to allogeneic myeloma vaccine plus Prevnar vaccine arm, Prevnar-13 will be
administered with each allogeneic myeloma vaccine. If assigned to either of the two arms that
do not include Prevnar, then patients will receive a placebo in lieu of Prevnar on the same
schedule. All patients will be followed for a minimum of 3 years.
Trial Arms
Name | Type | Description | Interventions |
---|
Lenalidomide plus GM-CSF Vaccine plus Prevnar13 | Experimental | Patients will continue on a standard dose of lenalidomide as a single agent until progression, or treatment limiting toxicity, following enrollment.
Patients assigned to vaccine therapy will receive injections on day 14 (+/-3 days) of cycles 1, 2, 3 and 6 from enrollment, and then annually thereafter. Prevnar vaccine will be administered with the GM-CSF vaccine administration. | - GM-CSF vaccine
- Lenalidomide
- Prevnar13
|
Lenalidomide Only | Placebo Comparator | Patients will continue on a standard dose of lenalidomide as a single agent until progression, or treatment limiting toxicity, following enrollment. Patients will also get placebo GM-CSF vaccine and placebo prevnar13. Placebo will be saline. | |
Lenalidomide plus GM-CSF Vaccine | Placebo Comparator | Patients will continue on a standard dose of lenalidomide as a single agent until progression, or treatment limiting toxicity, following enrollment.
Patients assigned to vaccine therapy will receive injections on day 14 (+/-3 days) of cycles 1, 2, 3 and 6 from enrollment, and then annually thereafter. Patients will also be administered a placebo prevnar13 vaccination. Placebo will be saline. | - GM-CSF vaccine
- Lenalidomide
|
Eligibility Criteria
Inclusion Criteria:
- Myeloma eligibility criteria are the following:
- Near complete remission (nCR) for ≥ 3 months defined as no measurable M-spike, and a
positive serum immunofixation
- Or complete remission (CR) (no measurable M-spike, immunofixation negative and bone
marrow plasma cells <5%)
- NDMM or RMM in nCR or CR having completed a minimum of 6 cycles of a lenalidomide
based regimen for a minimum of ≥ 3 months
- NDMM or RMM a patients who have been off corticosteroids for ≥ 4 weeks
- Patients with NDMM or RMM who have had autologous stem cell transplant are eligible,
but must be ≥ 12 months from transplant
- All patients must be MRD positive at 10-4 or greater by NGS sequencing at enrollment
- Age >18 years
- ECOG 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 mg/dl
- ANC >1000/µL
- Platelet >100,000/µL
- Total bilirubin <= 1.5 x ULN
- AST (SGOT) and ALT (SGPT) <= 3 x ULN.
- Ability to comprehend and have signed the informed consent.
- Have previously agreed to continue on maintenance therapy with lenalidomide concurrent
with vaccine administration until disease progression, or clinical indication to cease
therapy.
- Disease free of prior malignancies for at least 5 years with exception of currently
treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of
the uterus, cervix or breast.
- All study participants must be registered into the mandatory Revlimid REMS® program,
and be willing and able to comply with the requirements of the REMS® program.
- Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the Revlimid REMS® program.
- 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 starting
lenalidomide with each cycle (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.
- Able to take prophylactic anticoagulation (aspirin 81 or 325 mg/daily or, for patients
intolerant to ASA, warfarin or low molecular weight heparin).
Exclusion Criteria:
- Disease progression after stopping corticosteroids as defined as the appearance of a
detectable serum or urine M-spike, or an absolute increase of >10 mg/dl between
involved and uninvolved light chains, in the absence of measurable serum or urine
M-protein .
- Patients who are MRD negative by NGS at screening.
- Patients with a known diagnosis of POEMS syndrome, plasma cell leukemia, CNS
involvement, non-secretory myeloma and amyloidosis
- High-risk myeloma defined by presence of at least one of the following defining
features on initial diagnostic, or most recent bone marrow biopsy:
- High risk chromosomal translocations by FISH: t(4;14), t(14;16), t(14;20),
- del(17p), del(1p), amplification 1q.;
- MyPRS GEP-70 high risk signature either from diagnosis or at time of registration for
the study;
- LDH > 300 U/L at diagnosis;
- Relapse from prior therapy within 12 months.
- 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 the last four weeks,
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 allogeneic myeloma vaccine
- History of an allogeneic transplant
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 2-year progression free survival |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Number of participants without disease progression at 2 years. |
Secondary Outcome Measures
Measure: | Response Conversion Rate |
Time Frame: | 3 years |
Safety Issue: | |
Description: | 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. |
Measure: | MRD Conversion Rate |
Time Frame: | 3 years |
Safety Issue: | |
Description: | Number of participants who convert from MRD (Minimal Residual Disease) positive status to MRD negative status as determined through next generation sequencing (NGS). |
Measure: | Time to Response |
Time Frame: | 3 Years |
Safety Issue: | |
Description: | 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. |
Measure: | Progression Free Survival (PFS) |
Time Frame: | 3 and 5 years |
Safety Issue: | |
Description: | Number of months without disease progression. |
Measure: | Evaluate toxicity of allogenic myeloma vaccine |
Time Frame: | 3 years |
Safety Issue: | |
Description: | Number of participants experiencing adverse events grade 3 or higher, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) |
Measure: | Measure tumor specific immunity and correlate with systemic immunity |
Time Frame: | 3 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial Keywords
- Lenalidomide
- M-spike negative
- GVax
- GM-CSF secreting myeloma vaccine
- MRD positive
Last Updated
December 19, 2020