Clinical Trials /

SVN53-67/M57-KLH Peptide Vaccine in Treating Patients With Newly Diagnosed Multiple Myeloma Receiving Lenalidomide Maintenance Therapy

NCT02334865

Description:

This phase I trial studies the safety of SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant together with sargramostim in treating patients with newly diagnosed multiple myeloma who are receiving lenalidomide maintenance therapy. Vaccines made from survivin peptide may help the body build an effective immune response to kill cancer cells that express survivin. Incomplete Freund's adjuvant may help stimulate the body's immune response to a vaccine treatment. Colony-stimulating factors, such as sargramostim, may increase the production of blood cells. Lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant and sargramostim before or after the start of lenalidomide maintenance therapy may be a better treatment for multiple myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SVN53-67/M57-KLH Peptide Vaccine in Treating Patients With Newly Diagnosed Multiple Myeloma Receiving Lenalidomide Maintenance Therapy
  • Official Title: A Phase I Study of Safety, Tolerability and Immunological Effects of SVN53-67/M57-KLH in Patients With Multiple Myeloma Receiving Lenalidomide Maintenance Therapy

Clinical Trial IDs

  • ORG STUDY ID: I 247913
  • SECONDARY ID: NCI-2014-02621
  • SECONDARY ID: I 247913
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT02334865

Conditions

  • Partial Response of Multiple Myeloma or Plasma Cell Leukemia
  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
Incomplete Freund's AdjuvantFreund's Incomplete Adjuvant, IFA, ISA-51, Montanide ISA 51, Montanide ISA-51Group A (vaccine and week-4 lenalidomide maintenance therapy)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidGroup A (vaccine and week-4 lenalidomide maintenance therapy)
Sargramostim23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, SargramostatinGroup A (vaccine and week-4 lenalidomide maintenance therapy)
SVN53-67/M57-KLH Peptide VaccineGroup A (vaccine and week-4 lenalidomide maintenance therapy)

Purpose

This phase I trial studies the safety of SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant together with sargramostim in treating patients with newly diagnosed multiple myeloma who are receiving lenalidomide maintenance therapy. Vaccines made from survivin peptide may help the body build an effective immune response to kill cancer cells that express survivin. Incomplete Freund's adjuvant may help stimulate the body's immune response to a vaccine treatment. Colony-stimulating factors, such as sargramostim, may increase the production of blood cells. Lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant and sargramostim before or after the start of lenalidomide maintenance therapy may be a better treatment for multiple myeloma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the toxicity profile of the SVN53-67/M57-KLH peptide (SVN53-67/M57-KLH
      peptide vaccine) in Montanide ISA 51 (incomplete Freund's adjuvant) plus GM-CSF
      (sargramostim) (vaccine), given before or after the start of lenalidomide maintenance in
      patients with multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To measure the immune responses induced by SVN53-67/M57-KLH with Montanide ISA 51 plus
      GM-CSF, either alone or with lenalidomide maintenance added either before or after the
      vaccine.

      TERTIARY OBJECTIVES:

      I. To collect preliminary data on therapeutic efficacy of this combination against multiple
      myeloma, including response rate, time to progression and disease progression slope.

      II. To test if human leukocyte antigen (HLA) types and survivin positivity affect the immune
      responses induced by SVN53-67/M57-KLH with Montanide ISA 51 plus GM-CSF.

      OUTLINE: Patients are assigned to 1 of 2 groups.

      GROUP A: Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant
      subcutaneously (SC) and sargramostim SC every 2 weeks at weeks 0, 2, 4, and 6 for up to 4
      doses and then receive a booster in week 12. Beginning in week 4, patients receive
      lenalidomide maintenance therapy orally (PO) once daily (QD) in the absence of disease
      progression or unacceptable toxicity.

      GROUP B: Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC
      and sargramostim SC every 2 weeks at weeks 4, 6, 8, and 10 for up to 4 doses and then receive
      a booster in week 16. Beginning in week 0, patients receive lenalidomide maintenance therapy
      PO QD in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 16, 20, and 24 weeks and
      then every 3 months for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Group A (vaccine and week-4 lenalidomide maintenance therapy)ExperimentalPatients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 0, 2, 4, and 6 for up to 4 doses and then receive a booster in week 12. Beginning in week 4, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
  • Incomplete Freund's Adjuvant
  • Lenalidomide
  • Sargramostim
  • SVN53-67/M57-KLH Peptide Vaccine
Group B (vaccine and week-0 lenalidomide maintenance therapy)ExperimentalPatients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 4, 6, 8, and 10 for up to 4 doses and then receive a booster in week 16. Beginning in week 0, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
  • Incomplete Freund's Adjuvant
  • Lenalidomide
  • Sargramostim
  • SVN53-67/M57-KLH Peptide Vaccine

Eligibility Criteria

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Patients with newly diagnosed multiple myeloma who have at least a partial response
             after induction therapy based on the International Working Group (IWG) Uniform
             Response Criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry

          -  Must be free of systemic infection; subjects with active infections (whether or not
             they require antibiotic therapy) may be eligible after complete resolution of the
             infection; subjects on antibiotic therapy must be off antibiotics for at least 7 days
             before beginning treatment

          -  Absolute neutrophil count >= 750/mm^3

          -  Platelet count >= 30,000/mm^3

          -  Creatinine clearance >= 30 mL/minutes

          -  Total bilirubin =< 2 mg/dL

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
             upper limit of normal (ULN)

          -  All study participants must be registered into the mandatory Revlimid Risk Evaluation
             and Mitigation Strategy (REMS)®, and be willing and able to comply with the
             requirements of the Revlimid REMS®

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS® program

          -  Able to take aspirin (81 or 325 mg) daily for prophylactic anticoagulation (patients
             intolerant to acetylsalicylic acid, ASA, may use warfarin or low molecular weight
             heparin or other anticoagulants as deemed appropriate by physician)

          -  Disease free of prior malignancies for > 2 years with exception of currently treated
             basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma "in situ" of
             the cervix or breast

          -  All study participants must have one of the HLA alleles: HLA-A*02, HLA-A*03, HLAA*11,
             or HLA-A*24

        Exclusion Criteria:

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form

          -  Pregnant or breast feeding females; (lactating females must agree not to breast feed
             while taking lenalidomide)

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study as determined by the Principal
             Investigator

          -  Chemotherapy, immunotherapy, radiotherapy, radiosurgery, interferon (e.g. Intron-A®),
             allergy desensitization injections, growth factors (e.g. Procrit®, Aranesp®,
             Neulasta®), interleukins (e.g. Proleukin®) or any investigational therapeutic
             medication within 4 weeks of study entry

          -  Known hypersensitivity to thalidomide, lenalidomide, Keyhole Limpet Hemocyanin (KLH),
             or granulocyte colony-macrophage stimulating factor (GM-CSF)

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs

          -  Known seropositive for or active viral infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are
             seropositive because of hepatitis B virus vaccine are eligible

          -  Any prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy or
             autoimmune disorders with visceral involvement

          -  Patients with a known diagnosis of plasma cell leukemia

          -  Systemic corticosteroid therapy > 2 mg of dexamethasone or equivalent per day at study
             entry

          -  Patients had prior autologous or allogeneic stem cell transplant; prior stem cell
             collection is allowed

          -  Life expectancy less than 4 months
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity profile of the SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant plus sargramostim, given before or after the start of lenalidomide maintenance
Time Frame:Up to 24 weeks
Safety Issue:
Description:The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to evaluate toxicity. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. The frequency of toxicities will also be tabulated for the regimen estimated to be the regimen-limiting toxicity.

Secondary Outcome Measures

Measure:Immune response using interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and multimer assays
Time Frame:Up to 24 weeks
Safety Issue:
Description:A responder is defined as a patient who has responded in either IFN-gamma ELISPOT or multimer assays. For both the ELISPOT and multimer assays, time course and magnitude of responses will be plotted and data will be treated using mixed-effect modeling. In addition, Kendall's tau-b will be used to determine whether ELISPOT and multimer responses are associated.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

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