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

• ClinicalTrials.gov Identifier: NCT02334865
• Recruitment Status: Active, not recruiting
• First Posted: January 8, 2015
• Last Update Posted: December 14, 2022
• Sponsor: Roswell Park Cancer Institute
• Collaborator: Celgene
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Tracking Information

• First Submitted Date: January 6, 2015
• First Posted Date: January 8, 2015
• Last Update Posted Date: December 14, 2022
• Actual Study Start Date: April 13, 2017
• Estimated Primary Completion Date: January 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 6, 2015)

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 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 6, 2015)

Immune response using interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and multimer assays [ Time Frame: Up to 24 weeks ]

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Biological: Incomplete Freund's Adjuvant
  Given SC
  Other Names:

  • Freund's Incomplete Adjuvant
  • IFA
  • ISA-51
  • Montanide ISA 51
  • Montanide ISA-51
• Other: Laboratory Biomarker Analysis
  Correlative studies
• Drug: Lenalidomide
  Given PO
  Other Names:

  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid
• Biological: Sargramostim
  Given SC
  Other Names:

  • 23-L-Leucinecolony-Stimulating Factor 2
  • DRG-0012
  • Leukine
  • Prokine
  • rhu GM-CFS
  • Sagramostim
  • Sargramostatin
• Biological: SVN53-67/M57-KLH Peptide Vaccine
  Given SC

Study Arms

• Experimental: Group A (vaccine and week-4 lenalidomide maintenance therapy)
  Patients 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.
  Interventions:

  • Biological: Incomplete Freund's Adjuvant
  • Other: Laboratory Biomarker Analysis
  • Drug: Lenalidomide
  • Biological: Sargramostim
  • Biological: SVN53-67/M57-KLH Peptide Vaccine
• Experimental: Group B (vaccine and week-0 lenalidomide maintenance therapy)
  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.
  Interventions:

  • Biological: Incomplete Freund's Adjuvant
  • Other: Laboratory Biomarker Analysis
  • Drug: Lenalidomide
  • Biological: Sargramostim
  • Biological: SVN53-67/M57-KLH Peptide Vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 6, 2015): 18
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 9, 2023
• Estimated Primary Completion Date: January 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02334865
• Other Study ID Numbers: I 247913; NCI-2014-02621 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); I 247913 ( Other Identifier: Roswell Park Cancer Institute )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Roswell Park Cancer Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Roswell Park Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Celgene

Investigators

• Principal Investigator: Jens Hillengass, MD, PhD; Roswell Park Cancer Institute

• PRS Account: Roswell Park Cancer Institute
• Verification Date: December 2022