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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Smoldering Multiple Myeloma
• Intervention / Treatment: Drug: Hiltonol; Drug: Citarinostat; Biological: PVX-410; Drug: Lenalidomide

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital of Cleveland- Seidman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PVX-410 + Citarinostat; Participants will receive: 6 biweekly doses of PVX-410; 6 biweekly doses of Hiltonol; 3 monthly cycles of Citarinostat	Drug: Hiltonol; Intramuscular injection of Hiltonol (1 mg) administered Biweekly at the time of PVX-410 administration; Other Names: Poly ICLC; Drug: Citarinostat; Citarinostat (180 mg) administered orally once daily on days 1-21 every 28 day cycle.; Other Names: CC-96241; Biological: PVX-410; PVX-410 Biweekly (0.8 mg) via subcutaneous injection
Experimental: PVX-410 + Citarinostat + Lenalidomide; Participants will receive: 6 biweekly doses of PVX-410; 6 biweekly doses of Hiltonol; 3 monthly cycles of Citarinostat; 3 monthly cycles of Lenalidomide	Drug: Hiltonol; Intramuscular injection of Hiltonol (1 mg) administered Biweekly at the time of PVX-410 administration; Other Names: Poly ICLC; Drug: Citarinostat; Citarinostat (180 mg) administered orally once daily on days 1-21 every 28 day cycle.; Other Names: CC-96241; Biological: PVX-410; PVX-410 Biweekly (0.8 mg) via subcutaneous injection; Drug: Lenalidomide; Lenalidomide (25 mg) administered orally once daily on days 1-21 every 28 day cycle.; Other Names: REVLIMID

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Celgene; OncoPep, Inc.
• Investigators: Principal Investigator: Noopur Raje, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2017
• Primary Completion (Estimated): September 15, 2024
• Study Completion (Estimated): September 15, 2024

Study Registration Dates

• First Submitted: August 28, 2016
• First Submitted That Met QC Criteria: August 31, 2016
• First Posted (Estimated): September 1, 2016

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Interferon Inducers; Histone Deacetylase Inhibitors; Lenalidomide; Poly ICLC; Citarinostat
• Other Study ID Numbers: 16-237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No