Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Disease Progression

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antiemetics

Dermatologic Agents

Gastrointestinal Agents

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Ondansetron

Cyclophosphamide

Immunomodulating Agents

Ipilimumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Treatment:

Cyclophosphamide 300 mg/m2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Nina Bhardwaj, MD,PhD

The purpose of this study is to see whether the combination of low-dose Cyclophosphamide and Anti-CTLA4 (Ipilimumab) will stop tumor growth in patients with advanced skin cancer. The investigators expect to see an increase in response rate of the combination over Anti-CTLA-4 alone and estimate a response rate of approximately 20 % in the proposed population.

The transient removal of CTLA-4-mediated inhibition (CTLA-4 blockade) can induce effective anti-tumor immunity. Efficacy of CTLA-4 blockade as a single agent has been shown in melanoma 53. It has been hypothesized that anti-CTLA-4 antibody might deplete Treg cells 54, inducing autoimmunity. However, patients receiving Ipilimumab have not shown a decrease in Treg number or function in peripheral blood 55.

This trial will answer the question if the combination of Anti-CTLA 4 (following a well established regimen of Ipilimumab) and Cyclophosphamide (given at immunomodulatory doses) will result in antitumor activity in patients with metastatic melanoma due to synergistic immunomodulating effects by overcoming tolerance.

CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma

Phase II Study of CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma

One of the tumor punch biopsy will be put in formalin for paraffin-embedding. The other tumor punch biopsy will be processed to obtain lysates to be used as antigens for the T cell assays. Two tumor punch biopsies (4mm in diameter) will be obtained before and after therapy (baseline and week 12, and optional during weeks 24, 36, and 48) if patients have accessible tumors.

Objective response rate (ORR) using mWHO RC. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Progression-free survival is measured from date of entry to date of 1st documented evidence of recurrence, confirmation of PD, or death (whichever is 1st). T regulatory cells are measured on D1 (pre CTX) \& D3 of each cycle.

Peripheral blood taken at baseline/various therapeutic time points/possibly maintenance cycles to evaluate T regulatory cells identified, serially monitored by polychromatic flow cytometry using FoxP3+/CD4+/CD127low/CD25hi markers.

Bristol-Myers Squibb

Icahn School of Medicine at Mount Sinai

Director, Tumor Vaccine Program

Treatment:

Cyclophosphamide 300 mg/m\^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimuab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Cyclophosphamide, Ipilimumab

Treatment:

Cyclophosphamide 300 mg/m\^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Age, Continuous

Sex: Female, Male

Cutaneous MM

Ocular MM

Unknown Primary MM

Malignant Melanoma (MM) site

Dr. Nina Bhardwaj

Stable disease

Progression of disease

The Anti-tumor Activity of the Combination of Low Dose Cyclophosphamide and CTLA-4 Blockade Using Objective Response Rate (ORR)

Primary Endpoint not met, study terminated, data not collected

Progression-free Survival

Tumor-specific T Cell Responses Will be Measured in a Subset of Patients Who Have Biopsy Accessible Tumor and Have Tumor Biopsies Taken.

T Regulatory Cell Profile in Peripheral Blood

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Recurrence

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Microsatellite Instability

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Genomic Instability

Ovarian Cancer

Ovarian Epithelial Cancer

Pembrolizumab

BIRC5 protein, human

DPX-Survivac, Cyclophosphamide, Pembrolizumab

DPX-Survivac

This study will assess the safety and efficacy of DPX-Survivac and low dose cyclophosphamide with pembrolizumab in subjects with selected advanced and recurrent solid tumours.

This study is a Phase 2 with safety lead-in study to assess the safety and efficacy of DPX-Survivac, low dose cyclophosphamide, and pembrolizumab combination therapy in subjects with selected advanced and recurrent solid tumours. Two ovarian cancer arms will be recruited and randomized in this study, one with and one without cyclophosphamide. All other cohorts will be single arm, receiving treatment with the triple combination.

Up to 20 subjects, from any cohort, will be enrolled to assess the safety of study treatments before the study moves to the expansion phase. Once the safety lead-in is completed, the five cohorts will be expanded to recruit additional subjects following a Simon two stage design. Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms.

Study of an Immunotherapeutic, DPX-Survivac, in Combination With Low Dose Cyclophosphamide & Pembrolizumab, in Subjects With Selected Advanced & Recurrent Solid Tumors

A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment, DPX-Survivac in Combination With Low Dose Cyclophosphamide and Pembrolizumab, in Subjects With Selected Advanced and Recurrent Solid Tumours.

As measured by antigen specific immune response in peripheral blood

As measured by multiplex immunohistochemistry

Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Merck Sharp & Dohme LLC

ImmunoVaccine Technologies, Inc. (IMV Inc.)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma	NCT01740401	Melanoma	Cyclophosphamid...	18 Years -	Icahn School of Medicine at Mount Sinai
Study of an Immunotherapeutic, DPX-Survivac, in Combination With Low Dose Cyclophosphamide & Pembrolizumab, in Subjects With Selected Advanced & Recurrent Solid Tumors	NCT03836352	Ovarian Cancer Hepatocellular ... Non-small Cell ... Bladder Cancer Microsatellite ...	DPX-Survivac Cyclophosphamid... Pembrolizumab	18 Years -	ImmunoVaccine Technologies, Inc. (IMV Inc.)
CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma	NCT01740401	Melanoma	Cyclophosphamid...	18 Years -	Icahn School of Medicine at Mount Sinai

Spots Global Cancer Trial Database for t cell activation