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

This study is currently recruiting participants.
Verified January 2017 by Noopur Raje, Massachusetts General Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02886065
First Posted: September 1, 2016
Last Update Posted: January 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Celgene
OncoPep, Inc.
Information provided by (Responsible Party):
Noopur Raje, Massachusetts General Hospital
  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
  • Durvalumab
  • PVX-410

Condition Intervention Phase
Smoldering Multiple Myeloma Drug: Hiltonol Drug: Durvalumab Drug: Lenalidomide Biological: PVX-410 Phase 1

Study Type: Interventional
Study Design: 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 Durvalumab (Anti-PDL1) With and Without Lenalidomide for Patients With Smoldering Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Noopur Raje, Massachusetts General Hospital:

Primary Outcome Measures:
  • Determine The Safety And Tolerability Of The PVX-410 [ Time Frame: 2 years ]
    The CTCAE version 4.03 criteria will be used to grade toxicity


Secondary Outcome Measures:
  • Immune Responses Of Lymphocytes To HLA A2+ [ Time Frame: 2 years ]
  • Change In Monoclonal (M) Serum Protein [ Time Frame: 2 years ]
  • Change In Free Light Chain (FLC) [ Time Frame: 2 years ]
  • Change In Urinary FLC Level [ Time Frame: 2 years ]

Estimated Enrollment: 26
Study Start Date: November 2016
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Durvalumab Alone
Patients will receive 3 monthly infusions of Durvalumab
Drug: Durvalumab
Experimental: PVX-410+Durvalumab
  • Patients will receive 6 doses of PVX-410 Biweekly
  • 3 monthly infusions of Durvalumab
  • 6 doses of Hiltonol administered Biweekly
Drug: Hiltonol
Other Name: Poly ICLC
Drug: Durvalumab Biological: PVX-410
Experimental: PVX-410+Durvalumab +Lenalidomide
  • Patients will receive 6 doses of PVX-410 Biweekly via injection
  • 3 monthly infusions of Durvalumab
  • 6 doses of Hiltonol administered Biweekly
  • 3 course of Lenalidomide every 28 days
Drug: Hiltonol
Other Name: Poly ICLC
Drug: Durvalumab Drug: Lenalidomide
Other Name: REVLIMID
Biological: 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 vaccine in Combination with Lenalidomide is being used to hopefully provide immunity against Myeloma. Durvalumab is a check point inhibitor which is being combined here to further augment the immune activity of the vaccine. It is a monoclonal antibody known to take the brakes off the immune system to restore immunity. Lenalidomide in previously studied trials has demonstrated an increase in immune activity. It is the hope of the investigators the combination of the vaccine, Lenalidomide, and Durvalumab will augment immunity even further.

The FDA (the U.S. Food and Drug Administration) has not approved PVX-410 as a treatment for any disease.Durvalumab is also not approved for the treatment of Multiple Myeloma.

The FDA (the U.S. Food and Drug Administration) has approved Lenalidomide as a treatment option for Smoldering Multiple Myeloma

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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+ (Double and Triple Combination Cohorts only).
  • 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 PD1 or PD-L1 inhibitor, including durvalumab.
  • 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 durvalumab, 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.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • History of hypersensitivity to durvalumab or any excipient
  • 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02886065


Contacts
Contact: Noopur Raje, MD 617-726-0711

Locations
United States, Massachusetts
Massachusetts general Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Noopur Raje, MD    617-726-0711      
Principal Investigator: Noopur Raje, MD         
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     History of Changes
Other Study ID Numbers: 16-237
First Submitted: August 28, 2016
First Posted: September 1, 2016
Last Update Posted: January 19, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Noopur Raje, Massachusetts General Hospital:
Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
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
Lenalidomide
Thalidomide
Antibodies, Monoclonal
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Interferon Inducers