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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lenalidomide
Allogeneic Myeloma Vaccine
Prevnar-13
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Myeloma Vaccine, Prevnar, & Lenalidomide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Effect on Clonogenic Myeloma Precursors
Measures of stem cell population and plasma cell population.
Grade 3-4 Toxicity
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
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.

Full Information

First Posted
May 5, 2011
Last Updated
January 14, 2019
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01349569
Brief Title
Allogeneic GM-CSF Vaccine and Lenalidomide in Treating Myeloma Patients With Near Complete Remission
Official Title
Administration of an Allogeneic Myeloma GM-CSF Vaccine in Conjunction With a Lenalidomide Containing Regimen in Myeloma Patients With Near Complete Remission
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Myeloma Vaccine, Prevnar, & Lenalidomide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
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).
Intervention Type
Biological
Intervention Name(s)
Allogeneic Myeloma Vaccine
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Prevnar-13
Other Intervention Name(s)
Pneumococcal 13-Valent Conjugate Vaccine
Intervention Description
Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Primary Outcome Measure Information:
Title
Response Conversion Rate
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.
Time Frame
Up to 1 year
Secondary Outcome Measure Information:
Title
Time to Response
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.
Time Frame
Up to 4 years
Title
Effect on Clonogenic Myeloma Precursors
Description
Measures of stem cell population and plasma cell population.
Time Frame
Baseline, Cycle 3 Day 14, Cycle 6 Day 14, and 1 year
Title
Grade 3-4 Toxicity
Description
Number of participants who experienced grade 3-4 toxicity as per CTCAE 4.0.
Time Frame
Up to 1 year
Title
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ivan Borrello, M.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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