Clinical Trials /

A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM

NCT02886065

Description:

This research study is studying a targeted therapy as a possible treatment for Smoldering Multiple Myeloma. The following intervention will be involved in this study: - Lenalidomide - Citarinostat (CC-96241) - PVX-410

Related Conditions:
  • Smoldering Plasma Cell Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM
  • Official Title: A Phase 1b Study of PVX-410, a Multi-Peptide Cancer Vaccine, and Citarinostat (CC-96241), a Histone Deacetylase Inhibitor (HDAC) With and Without Lenalidomide for Patients With Smoldering Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 16-237
  • NCT ID: NCT02886065

Conditions

  • Smoldering Multiple Myeloma

Interventions

DrugSynonymsArms
HiltonolPoly ICLCPVX-410 + Citarinostat
CitarinostatCC-96241PVX-410 + Citarinostat
LenalidomideREVLIMIDPVX-410 + Citarinostat + Lenalidomide
PVX-410PVX-410 + Citarinostat

Purpose

This research study is studying a targeted therapy as a possible treatment for Smoldering Multiple Myeloma. The following intervention will be involved in this study: - Lenalidomide - Citarinostat (CC-96241) - PVX-410

Detailed Description

      This research study is a Phase I clinical trial, which tests the safety of an investigational
      intervention and also tries to define the appropriate dose of the investigational
      intervention to use for further studies. "Investigational" means that the intervention is
      being studied.

      In this research study, the investigators are studying Smoldering Multiple Myeloma.
      Smoldering Multiple Myeloma is an early precursor to a rare blood cancer known as Multiple
      Myeloma, which affects plasma cells. The study will test two different combinations of the
      study drugs; a combination of the vaccine (PVX-410) along with Citarinostat (CC-96241) and
      triple combination of the vaccine, Citarinostat, and Lenalidomide.

      The vaccine (PVX-410) is a multi-peptide vaccine that contains four synthetic peptides that
      together are intended to induce a T cell-mediated immune response against the myeloma. The
      FDA (the U.S. Food and Drug Administration) has not approved PVX-410 as a treatment for any
      disease.

      Citarinostat is an orally active, small-molecule Histone Deacetylase (HDAC) Inhibitor which
      is being combined here to further augment the immune activity of the vaccine. Citarinostat
      has not been approved by the FDA as a treatment for any disease.

      Lenalidomide is commercially available analogue of thalidomide with immunomodulatory,
      antiangiogenic, and antineoplastic properties that has demonstrated an increase in immune
      activity in previous trials. The FDA has approved Lenalidomide as a treatment option for
      Smoldering Multiple Myeloma. Lenalidomide is being added to the combination of the vaccine
      and Citarinostat because it is hypothesized that co-administration of lenalidomide along with
      Citarinostat would further enhance the T cell-mediated immune response induced by PVX-410.
    

Trial Arms

NameTypeDescriptionInterventions
PVX-410 + CitarinostatExperimentalParticipants will receive: 6 biweekly doses of PVX-410 6 biweekly doses of Hiltonol 3 monthly cycles of Citarinostat
  • Hiltonol
  • Citarinostat
  • PVX-410
PVX-410 + Citarinostat + LenalidomideExperimentalParticipants will receive: 6 biweekly doses of PVX-410 6 biweekly doses of Hiltonol 3 monthly cycles of Citarinostat 3 monthly cycles of Lenalidomide
  • Hiltonol
  • Citarinostat
  • Lenalidomide
  • PVX-410

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has confirmed SMM according to a definition derived from the International
             Myeloma Working Group (IMWG) definition (International Working Group, 2003): serum
             M-protein ≥3 g/dL or BMPC >10%, or both, along with normal organ and marrow function
             (CRAB) within 4 weeks before baseline.

               -  C: Absence of hypercalcemia, evidenced by a calcium <10.5 mg/dL.

               -  R: Absence of renal failure, evidenced by a creatinine < 1.5 mg/dL (177 µmol/L)
                  or calculated creatinine clearance (using the Modification of Diet in Renal
                  Disease [MDRD] formula) >50 mL/min.

               -  A: Absence of anemia, evidenced by a hemoglobin >10 g/dL.

               -  B: Absence of lytic bone lesions on standard skeletal survey.

          -  Patient is at higher than average risk of progression to active MM, defined as having
             2 or more of the following features:

               -  Serum M-protein ≥3 g/dL.

               -  BMPC >10%.

               -  Abnormal serum FLC ratio (0.26-1.65).

          -  Patient is aged 18 years or older.

          -  Patient has a life expectancy of greater than 6 months.

          -  Patient is HLA-A2+

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Patient has adequate bone marrow function, evidenced by a platelet count ≥75×109/L and
             an absolute neutrophil count (ANC) ≥1.0×109/L within 2 weeks before baseline.

          -  Patient has adequate hepatic function, evidenced by a bilirubin ≤2.0 mg/dL and an
             alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5×ULN within 2 weeks
             before baseline.

          -  If of child-bearing potential, patient agrees to use adequate birth control measures
             during study participation.

          -  If a female of child-bearing potential , patient has negative serum pregnancy test
             results within 2 weeks before baseline and is not lactating.

          -  If assigned to receive lenalidomide and a female of reproductive potential, must
             adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.

          -  If assigned to receive lenalidomide, patient must be registered into the mandatory
             Revlimid REMS® program and be willing and able to comply with the requirements of the
             REMS® program.

          -  Patient (or his or her legally accepted representative) has provided written informed
             consent to participate in the study.

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

        Exclusion Criteria:

          -  Patient has symptomatic MM, as defined by any of the following:

               -  Lytic lesions or pathologic fractures.

               -  Anemia (hemoglobin <10 g/dL).

               -  Hypercalcemia (corrected serum calcium > 11.5 mg/dL).

               -  Renal insufficiency (creatinine > 1.5 mg/dL).

               -  Other: symptomatic hyperviscosity, amyloidosis.

          -  Patient has a history of a prior malignancy within the past 3 years (excluding
             resected basal cell carcinoma of the skin or in situ cervical cancer).

          -  Patient has abnormal cardiac status, evidenced by any of the following:

               -  New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF).

               -  Myocardial infarction within the previous 6 months.

               -  Symptomatic cardiac arrhythmia requiring treatment or persisting despite
                  treatment.

          -  Patient is receiving any other investigational agent.

          -  Patient has a current active infectious disease or positive serology for human
             immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), or
             hepatitis A virus (HAV).

          -  Patient has a history of or current auto-immune disease.

          -  Patient has been vaccinated with live attenuated vaccines within 4 weeks before study
             vaccination.

          -  Any previous treatment with a HDAC inhibitor, including Citarinostat.

          -  Had involvement in the planning and/or conduct of the study by association with the
             Sponsor, study drug supplier(s) or study center or was previously enrolled in the
             present study.

          -  Current or prior use of immunosuppressive medication within 28 days before the first
             dose of treatment, with the exceptions of intranasal and inhaled corticosteroids or
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
             prednisone, or an equivalent corticosteroid.

          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
             electrocardiograms (ECGs) using Frediricia's Correction.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, active peptic ulcer disease or gastritis, active bleeding diatheses,
             or psychiatric illness/social situations that would limit compliance with study
             requirements or compromise the ability of the patient to give written informed consent

          -  Known history of previous clinical diagnosis of tuberculosis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety And Tolerability Of The PVX-410 Tumor Vaccine Regimen
Time Frame:2 years
Safety Issue:
Description:The proportion of participants who experience dose limiting toxicities and other toxicities. The CTCAE version 4 criteria will be used to grade adverse events.

Secondary Outcome Measures

Measure:Immune Responses Of Lymphocytes To HLA A2+
Time Frame:2 years
Safety Issue:
Description:
Measure:Change In Monoclonal (M) Serum Protein
Time Frame:2 years
Safety Issue:
Description:
Measure:Change In Free Light Chain (FLC)
Time Frame:2 years
Safety Issue:
Description:
Measure:Change In Urinary FLC Level
Time Frame:2 years
Safety Issue:
Description:
Measure:Correlation of Immune Response and Clinical Anti-tumor Responses
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Myeloma

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