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

• ClinicalTrials.gov Identifier: NCT02886065
• Recruitment Status: Active, not recruiting
• First Posted: September 1, 2016
• Last Update Posted: January 31, 2023
• Sponsor: Massachusetts General Hospital
• Collaborators: Celgene; OncoPep, Inc.
• Information provided by (Responsible Party): Noopur Raje, Massachusetts General Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Smoldering Multiple Myeloma	Drug: Hiltonol; Drug: Citarinostat; Drug: Lenalidomide; Biological: PVX-410	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: March 7, 2017
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: June 2023

Arms and Interventions

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 Name: Poly ICLC; Drug: Citarinostat; Citarinostat (180 mg) administered orally once daily on days 1-21 every 28 day cycle.; Other Name: 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 Name: Poly ICLC; Drug: Citarinostat; Citarinostat (180 mg) administered orally once daily on days 1-21 every 28 day cycle.; Other Name: CC-96241; Drug: Lenalidomide; Lenalidomide (25 mg) administered orally once daily on days 1-21 every 28 day cycle.; Other Name: REVLIMID; Biological: PVX-410; PVX-410 Biweekly (0.8 mg) via subcutaneous injection

Outcome Measures

Primary Outcome Measures :

1. Safety And Tolerability Of The PVX-410 Tumor Vaccine Regimen [ Time Frame: 2 years ]
   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 :

1. Immune Responses Of Lymphocytes To HLA A2+ [ Time Frame: 2 years ]
2. Change In Monoclonal (M) Serum Protein [ Time Frame: 2 years ]
3. Change In Free Light Chain (FLC) [ Time Frame: 2 years ]
4. Change In Urinary FLC Level [ Time Frame: 2 years ]
5. Correlation of Immune Response and Clinical Anti-tumor Responses [ Time Frame: 2 years ]

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts general Hospital

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02115

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, New York

Weill Cornell Medical College

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

University Hospital of Cleveland- Seidman Cancer Center

Cleveland, Ohio, United States, 44106

Sponsors and Collaborators

Massachusetts General Hospital

Celgene

OncoPep, Inc.

Investigators

• Principal Investigator: Noopur Raje, MD; Massachusetts General Hospital

More Information

• Responsible Party: Noopur Raje, MD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02886065
• Other Study ID Numbers: 16-237
• First Posted: September 1, 2016
• Last Update Posted: January 31, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Noopur Raje, Massachusetts General Hospital:

Myeloma

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia; Lenalidomide; Poly ICLC; Citarinostat; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents; Interferon Inducers; Histone Deacetylase Inhibitors; Enzyme Inhibitors