Vaccination With Flt3L, Radiation, and Poly-ICLC

NCT03789097 | Unknown Phase 1 DMC FDA Drug

• 2 other identifiers: GCO 19-0477GCO 18-2394
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a combination of 4 therapies, three of which are used to treat a single "target site" of your cancer (such as a lymph node or a single tumor), and the 4th is given directly into the blood stream (intravenous or "IV").

1. 1.Radiation: The target site --lymph node or tumor (the one what will be injected) --will get two small treatments of radiation. Radiation is often times used to shrink and kill tumors in patients with certain types of lymphoma, breast cancer and head and neck cancer, however, the dose of radiation that you will receive --one dose on day one of the clinical trial and one dose on day two --is 10 to 20 time less radiation that you would receive for treatment of these cancers.
2. 2.Flt3L/CDX-301 is an immune cell growth factor, similar to white blood cell growth factors (Neupogen or Neulasta) or red blood cell growth factors (EPO or Epogen) that you may have received to help protect your blood cells previously. Flt3L causes your body to make more immune cells, specifically a type of immune cell called "dendritic cells".
3. 3.Poly-ICLC is an immune cell activating factor. Its function is to turn on the immune cells that have been brought to the tumor by Flt3L.
4. 4.Pembrolizumab is an antibody (a type of human protein) that is being tested to see if it will allow the body's immune system to kill your tumor cells. Pembrolizumab is approved for use by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with many different types of cancer including head and neck cancer. Pembrolizumab is not FDA approved to treat patients with non-Hodgkin's lymphoma or metastatic breast cancer, as it has not been effective at treating these cancers when used alone. While most people do not have immediate side effects when this medication is given, it has the ability to cause side effects for.

Conditions

Non-Hodgkin's Lymphoma; Metastatic Breast Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

Radiation; Poly-ICLC; Pembrolizumab; Lymphoma; Breast Cancer; Carcinoma

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  DLTs recorded and graded according to NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03, within DLT evaluation window of 63 days (end of cycle 1 of pembrolizumab) from initiation of in situ vaccine.

  63 days

Secondary Outcomes (1)

• Overall response rate (ORR)

  6 months

Study Arms (1)

Combination therapy

EXPERIMENTAL

Vaccination with Flt3L, Radiation, and Poly ICLC combined with Pembrolizumab

Drug: Pembrolizumab; Drug: Flt3L; Radiation: Radiation; Drug: Poly ICLC

Interventions

Pembrolizumab DRUG

200 mg administered as an IV infusion over 30 minutes Q3W

Also known as: Keytruda

Combination therapy

Flt3L DRUG

an immune cell growth factor. CDX-301 drug product is formulated as a sterile solution intended for single-use parenteral administration. Each vial contains a nominal 2.5 mg/mL CDX-301 protein in a 1 mL volume of buffered solution composed of sodium phosphate and sodium chloride, with a pH of 7.0.

Also known as: CDX-301, Recombinant Human Flt3 Ligand

Combination therapy

Radiation RADIATION

The target site will get 2 small treatments of radiation.

Combination therapy

Poly ICLC DRUG

an immune cell activating factor. vials containing 1 ml of 2 mg/mL

Also known as: Hiltonol

Combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have pathologically confirmed iNHL, MBC or HNSCC
• Lymphoma subtypes that may be enrolled include small lymphocytic lymphoma

You may not qualify if:

• Is currently participating and receiving an investigational therapy (not standard therapies) or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
• Any patients that require immediate treatment or cytoreduction are excluded. Note: This is applicable for iNHL, MBC, and HNSCC populations.
• Any patient with transformed lymphoma, or patients with grade 3A follicular lymphoma are excluded.
• MZL patients with gastric MALT lymphomas with disease localized to the stomach are excluded, and any patient with disease in a site where injection is determined to be high risk.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
• Hypersensitivity to pembrolizumab, poly-ICLC, Flt3L or any of their excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to study D22 (First dose of pembrolizumab) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to agents administered more than 28 days before initiation of in situ vaccine protocol.
• Has had prior chemotherapy, targeted small molecule therapy, or RT therapy within 14 days prior to study D0 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to a previously administered agent. Note: Patients with chronic ≤ Grade 2 AEs such as neuropathy are an exception to this criterion and may qualify for the study.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has known active central nervous system metastases, leptomeningeal disease and/or lymphomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include leptomeningeal disease or lymphomatous meningitis, which are excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a systemic treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy at time of enrollment in trial.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical or anal cancer, prostate cancer on stable dose of hormonal therapy without rising PSA.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Merck Sharp & Dohme LLC: collaborator
• Celldex Therapeutics: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Lymphoma; Carcinoma

Interventions

pembrolizumab; Radiation; poly ICLC

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Joshua Brody, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martine Van Voorthuysen

CONTACT

(212) 824-7822; Martine.VanVoorthuysen@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 26, 2018
• First Posted: December 28, 2018
• Study Start: April 5, 2019
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: January 30, 2024

Record last verified: 2024-01

Locations

US (1)