Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Squamous Cell

Lymphoma

Lymphoma, Non-Hodgkin

Squamous Cell Carcinoma of Head and Neck

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Breast Diseases

Skin Diseases

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Anti-Infective Agents

Pembrolizumab

Poly ICLC

Mitogens

Flt3 ligand protein

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Interferons

Immunologic Factors

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

200 mg administered as an IV infusion over 30 minutes Q3W

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.

Flt3L

The target site will get 2 small treatments of radiation.

Radiation

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

Martine Van Voorthuysen

Joshua Brody

Joshua Brody, MD

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. 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. 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. 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. 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.

Phase 1 and Phase 2 will occur sequentially:

Phase 1 is the preliminary safety assessment portion of the study, which will follow a modified 3 + 3 design to assess toxicity. The trial would be held for review should there be more than 1 dose-limiting toxicity (DLT) observed within the first 3-6 patients. The toxicity of the in situ vaccine without pembrolizumab (ongoing and previous trials) has been minimal, limited to transient febrile response to the intratumoral Toll-like receptor (TLR) ligand poly-ICLC, typically resolving with oral acetaminophen. As such, the primary objective of Phase 1 is to assess the safety of the addition of pembrolizumab to this in situ vaccine protocol. In Phase 1, patients will only be enrolled at the lead institution (Mount Sinai). After enrollment of the initial 3 patients, enrollment will pause until all three patients have completed cycle 1 of pembrolizumab (DLT evaluation window is 63 days from initiation of in situ vaccine). During the pause, new patients may be consented and screened, but not initiated on therapy. If 1 or no DLTs are observed in the first 3 patients, an additional 3 patients will be enrolled. The regimen will be considered safe (in order to progress to Phase 2) if no more than 1 out of 6 patients experience a DLT. If two or more DLTs are observed at any point in Phase 1 then accrual will be stopped for protocol review by Data Safety Monitoring Board, PIs and sponsor for possibility of protocol amendment.

Phase 2 will follow a Simon's two-stage design. This Phase will proceed only if toxicity is acceptable as determined in Phase 1.

Phase 1/2 design: Patients will be enrolled concurrently into three independent cohorts, with patients from Phase 1 evaluated within their subsequent disease-specific cohorts. iNHL, MBC and HNSCC often have peripherally accessible tumors amenable to intratumoral injection, and have all had relatively modest responses to single-agent checkpoint blockade, so are good candidates for this novel combination. Patients will be enrolled regardless of the PD-L1 staining of their tumor. We will also enroll patients previously exposed to PD-1/PD-L1 targeted therapies either on a clinical trial or as standard of care (as for HNSCC).

Cohort A: iNHL including but not limited to chronic lymphocytic leukemia (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). This cohort excludes patients with diffuse large B cell lymphoma (DLBCL) and any other lymphoma determined to be progressing rapidly by investigator (PI or site PI).

Cohort B: MBC with peripherally palpable disease amenable to intratumoral injection.

Cohort C: HNSCC with peripherally palpable disease amenable to intratumoral injection.

Stage 1: Seven patients will be evaluated in Stage 1 of Phase 2 in each disease-specific cohort, inclusive of patients enrolled in Phase 1. If no patient in a cohort achieves a response, the study in that cohort will close due to a lack of efficacy. The first seven patients in each histology will only be enrolled at Mount Sinai.

Stage 2: If one or more responses are seen in Stage 1, enrollment of an additional 12 patients for Cohorts A and B or 11 patients for Cohort C will proceed. These cohorts may be also be enrolled at collaborator sites (to be determined).

* Cohorts A or B: If at least three out of the 19 patients achieve a response, the intervention will be considered promising and worthy of further investigation.
* Cohort C: If at least four out of the 18 patients achieve a response, the intervention will be considered promising and worthy of further investigation.

Vaccination With Flt3L, Radiation, and Poly-ICLC

In Situ Vaccination With Flt3L, Radiation, and Poly-ICLC Combined With Pembrolizumab in Patients With Non-Hodgkin's Lymphoma, Metastatic Breast Cancer, and Head and Neck Squamous Cell Carcinoma

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.

Overall response rate (ORR) as defined as best response achieved within the first 6 months from initiation of trial. ORR is defined as complete remission (CR) or partial remission (PR) in patients as defined by RECIST v1.1 for MBC and HNSCC or as per the RECIL Criteria for patients with lymphoma, determined by Positron emission tomography-computed tomography (PET/CT) or computed tomography (CT) imaging which occurs at 3 month intervals, with the first imaging 3 months following initiation of Flt3L (D0) +/- 2 weeks.

Merck Sharp & Dohme LLC

Celldex Therapeutics

Icahn School of Medicine at Mount Sinai

Assistant Professor

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Mouth and Tooth Diseases

Heart and Blood Diseases

Carcinoma, Non-Small-Cell Lung

Stomach Neoplasms

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Esophageal Neoplasms

Pancreatic Neoplasms

Adenocarcinoma

Cholangiocarcinoma

Leukemia

Leukemia, Lymphoid

Melanoma

Carcinoma, Renal Cell

Liver Neoplasms

Carcinoma, Transitional Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Mouth Neoplasms

Kidney Neoplasms

Waldenstrom Macroglobulinemia

Fallopian Tube Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Hematologic Diseases

Fallopian Tube Diseases

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Liver Diseases

Stomach Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Esophageal Cancer

Pancreatic Cancer

Bile Duct Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Fallopian Tube Cancer

Oral Cancer

Laryngeal Cancer

Indolent B Cell Lymphoma

Lip and Oral Cavity Cancer

Hematinics

Gastrointestinal Agents

Amino Acids

Antibodies

Paclitaxel

Gemcitabine

Albumin-Bound Paclitaxel

Immunoglobulins

Liver Extracts

Pancrelipase

Pancreatin

Tyrosine

Part 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.

Part 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.

Part 3: Eligible patients will receive CDX-1140, based on cohort assigned, in 3 week cycles until progression, or intolerance, or two years of treatment. A fixed dose of pembrolizumab will also be given in 3 week cycles.

Part 4: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, or intolerance, or two years of treatment. Chemotherapy will also be given according to standard of care.

CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

CDX-1140

CDX-301 will be injected once a day for five days before Cycles 1 and 2.

CDX-301

pembrolizumab will be administered every 3 weeks.

pembrolizumab

Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.

Chemotherapy

This is a study to determine the maximum tolerated dose (MTD) for CDX-1140 (CD40 antibody), either alone or in combination with CDX-301 (FLT3L), pembrolizumab, or chemotherapy and to further evaluate its tolerability and efficacy in expansion cohorts once the MTD is determined.

This study will determine the MTD of CDX-1140 while also evaluating the safety, tolerability and efficacy of CDX-1140 alone (Part 1) or in combination with CDX-301 (Part 2), pembrolizumab (Part 3), or chemotherapy (Part 4) in patients with cancer.

Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-1140. The dose-escalation part of the study will test the safety profile of CDX-1140, alone or in combination with CDX-301, pembrolizumab or chemotherapy and determine which dose(s) of CDX-1140 will be studied in the expansion portions of the study.

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies

A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies

The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.

The percentage of patients who achieved a confirmed complete response or partial response by evaluation criteria in solid tumors for immune-based therapeutics (iRECIST; for solid tumor patients) and the lymphoma response to immunomodulatory therapy criteria (LYRIC; for lymphoma patients).

The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months

The interval from which measurement criteria are first met for CR or PR until the first date that progressive disease is objectively documented

The time from start of study drug to time of progression or death, whichever occurs first

The time from start of study drug to death

Serum samples will be obtained for assessment of human anti-CDX-1140 and anti-CDX-301 antibodies

CDX-1140 and CDX-301 concentrations will be measured

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vaccination With Flt3L, Radiation, and Poly-ICLC	NCT03789097	Non-Hodgkin's L... Metastatic Brea... Head and Neck S...	Pembrolizumab Flt3L Radiation Poly ICLC	18 Years -	Icahn School of Medicine at Mount Sinai
A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies	NCT03329950	Melanoma Non-small Cell ... Breast Cancer Gastric Cancer Renal Cell Carc... Ovarian Cancer Cholangiocarcin... Bladder Urothel... Pancreatic Aden... Colorectal Canc... Esophageal Canc... Hepatic Cancer Head and Neck C... Primary Periton... Fallopian Tube ... Other Solid Tum... Diffuse Large B... Mantle Cell Lym... Indolent B-cell... Non-Hodgkin Lym... Follicular Lymp... Lymphoplasmacyt... Waldenstrom's D... Marginal Zone L... Mucosa Associat... Small Lymphocyt...	CDX-1140 CDX-301 pembrolizumab Chemotherapy	18 Years -	Celldex Therapeutics
A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies	NCT03329950	Melanoma Non-small Cell ... Breast Cancer Gastric Cancer Renal Cell Carc... Ovarian Cancer Cholangiocarcin... Bladder Urothel... Pancreatic Aden... Colorectal Canc... Esophageal Canc... Hepatic Cancer Head and Neck C... Primary Periton... Fallopian Tube ... Other Solid Tum... Diffuse Large B... Mantle Cell Lym... Indolent B-cell... Non-Hodgkin Lym... Follicular Lymp... Lymphoplasmacyt... Waldenstrom's D... Marginal Zone L... Mucosa Associat... Small Lymphocyt...	CDX-1140 CDX-301 pembrolizumab Chemotherapy	18 Years -	Celldex Therapeutics

Spots Global Cancer Trial Database for flt3l

Every month we try and update this database with for flt3l cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for flt3l

Every month we try and update this database with for flt3l cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for flt3l cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.