Allogeneic Myeloma GM-CSF Vaccine With Lenalidomide in Multiple Myeloma Patients in Complete or Near Complete Remission

Study 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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03376477
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Syed A Ali, MD
Principal Investigator Affiliation Johns Hopkins University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustryIndustry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

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.

Arms & Interventions

Arms

Experimental: Lenalidomide plus GM-CSF Vaccine plus Prevnar13

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.

Placebo Comparator: Lenalidomide Only

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.

Placebo Comparator: Lenalidomide plus GM-CSF Vaccine

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.

Interventions

Biological: - GM-CSF vaccine

Each vaccination will consist of three total intra-dermal injections, on day 14 of cycles 1, 2, 3, 6 and annually for a minimum of 36 months in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). In the event that the specified limb is contraindicated, the dominant arm may be used. Vaccine injection sites shall be at least 5 cm at needle entry from the nearest neighbor. The approximate volume of each vaccination injection is approximately 0.7-0.8ml.

Drug: - Lenalidomide

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).

Drug: - Prevnar13

Prevnar will be administered at the same time points as the GM-CSF vaccine (day 14 of cycles 1, 2, 3, 6 and annually for a minimum of 36 months), but on the opposite arm from GM-CSF vaccine.

Other: - Placebo Prevnar13

Saline will be used for placebo. Placebo prevnar will be administered at the same time points as the GM-CSF vaccine or Placebo GM-CSF Vaccine (day 14 of cycles 1, 2, 3, 6 and annually for a minimum of 36 months), but on the opposite arm from GM-CSF vaccine or placebo GM-CSF vaccine.

Other: - Placebo GM-CSF Vaccine

Saline will be used for placebo. Each placebo vaccine will consist of three total intra-dermal injections on day 14 of cycles 1, 2, 3, 6 and annually for a minimum of 36 months in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). In the event that the specified limb is contraindicated, the dominant arm may be used. Placebo injection sites shall be at least 5 cm at needle entry from the nearest neighbor. The approximate volume of each injection is approximately 0.7-0.8ml.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Baltimore, Maryland

Status

Recruiting

Address

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287

Site Contact

Syed A Ali, MD

sali35@jhmi.edu

443-287-7104