Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

All Drugs and Chemicals

Immunomodulating Agents

Subjects participating in this study will receive a single dose of 1x10\^8, 3x10\^8, or 1x10\^9 autologous Ad-ISF35-transduced CLL B cells.

ISF35

William G. Wierda, M.D., Ph.D.

The study is a Phase I, dose-escalating, non-randomized, single institution clinical trial assessing the safety and efficacy of autologous Ad-ISF35-transduced CLL B cells administered as a single intravenous infusion in patients with chronic lymphocytic leukemia (CLL).

Memgen's first TNF family derived product, ISF35, is a gene that encodes a recombinant protein molecule that binds and activates human CD40+ B lymphocytes that are found on a vast majority of malignant leukemias and lymphomas.

In this clinical trial, ISF35 will be introduced into the patients' CLL cells ex vivo using a replication-defective adenovirus Ad5 encoding the ISF35 cDNA transgene. After this ex vivo manipulation, the modified leukemia cells will be extensively washed and the amount of remaining free virus is measured before the cells are reinfused into the patient. Following ex vivo transduction, the CLL cells expressing ISF35 activate a therapeutic immune response directed against the target leukemia cells.

This ascending-dose trial will be divided into three dosing cohorts to determine the existence of a maximum tolerated dose.

Patients will be followed for 12 months after ISF35 administration or until initiation of another treatment.

A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)

Memgen, LLC

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

The dose escalation phase will include rAd.CD40L dose escalation and increase in the number of injected sites/lesions. Once patients tolerate dose level 1 (1 injection site and 1x1011vp-MTD) in Dose Escalation cohort, Expansion cohort will open with same maximum number of injection sites at maximum tolerated dose from Dose Escalation cohort.

All participants receive same dosage of Pembrolizumab in both phases.

Dose Escalation Phase Starting Dose: 5x10\^10 vp per tumor as an injection directly into 1-3 tumors every 3 weeks. Same tumors injected for each of the 4 injections at week 0, 3, 6 and 9. If the dose well tolerated, the rAd.CD40L escalated to 1x10\^11 vp. Subsequently enrolled patients injected at the same dose of 1x10\^11 vp. Number of injected sites/tumors increased to two sites/lesions if patients have \>/=2 injectable lesions, at the same injection dose of 1x10\^10 up to three separate sites/lesions if patients have \> 3 injectable lesions.

Dose Expansion Phase Starting Dose: MTD from Dose Escalation Phase.

rAd.CD40L

Dose Escalation and Expansion Phases: 2 mg/kg by vein every 3 weeks.

Adi Diab, MD

The goal of this clinical research study is to find the highest tolerated dose of rAd.CD40L (also called ISF35) when given with pembrolizumab to patients with melanoma. Researchers also want to learn if the highest tolerated dose of ISF35 and pembrolizumab can help to control the disease.

The safety of this drug combination will be also be studied.

Study Groups:

If participant is found to be eligible to take part in this study, they will be assigned to 1 of 2 dose levels of ISF35 based on when they join this study. Up to 6 participants will be enrolled in the first group and up to 24 participants will be enrolled in the second group. The first group of participants will receive the lowest dose level. If no intolerable side effects are seen, all other participants enrolled in the study will receive the highest dose. If participant is assigned to the first group, they will not be able to move up to the second group.

All participants will also receive the same dose of pembrolizumab.

Study Drug Administration:

Participants will receive ISF35 as an injection directly into 1-3 tumors every 3 weeks. The injections will be done in the clinic or at the interventional radiology suite. The study staff may use image guidance such as ultrasound, CT, and/or MRI to help inject the drug into the tumor.

Participants will also receive pembrolizumab by vein over about 30 minutes every 3 weeks.

Study Visits:

At Week 0 (the first week participants receive treatment):

* Participant will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests and to check participant's immune system.
* Participant will have a tumor biopsy to check how the disease is responding to the study drug. To collect a biopsy, the area of skin is numbed with anesthetic and a small cut is made to remove all or part of the affected tissue. This biopsy will be performed within 24 hours of the first dose.
* The tumors will be photographed and measured. For the photographs, participant's private areas will be covered (as much as possible), and a picture of their face will not be taken unless there are tumors on their face.

At Weeks 1 and 2:

* Participant will have a physical exam.
* Blood (about 1 teaspoon) will be drawn for routine tests.

At Weeks 3, 6, and 9 (± 3 days):

* Participant will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests and to check participant's immune system.
* During Week 6 only, participant will have a biopsy of 1 of the tumors that has been injected with the study drug and 1 of the tumors that they did not have an injection in to learn if the tumors have responded to the study drug. Researchers also want to learn if participant has any genetic mutations (changes) that may change how they respond to the study drug. The tumors will also be photographed and measured.

Length of Study:

Participant may receive the study drugs for up to 9 weeks. Participant will be taken off study if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over after about 2 years of follow-up visits.

End-of-Study Visit:

About 3 weeks after participant's last dose of study drug (Week 12) or as soon as they stop taking the study drug (if they stop taking the study drug before Week 9):

* Participant will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests, to check participant's immune system, and to learn if the study drug has had any effect on the disease.
* Participant will have an MRI, CT, or positron emission computed tomography (PET)/CT scan and the tumors will be photographed and measured.

Follow-Up

Within 2 weeks after participant's last dose of study drugs and then every 8-12 weeks after that for up to 2 years:

* Participant will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests, to check participant's immune system, and to learn if the study drug has had any effect on the disease.
* Participant will have MRI, CT, and/or PET/CT scans to check the status of the disease. The tumors will also be measured and photographed. Participant's doctor will decide what type of scans they will have.
* At participant's first follow-up visit after they stop taking the study drug, they will have a tumor biopsy to check the status of the disease.

If participant chooses to receive care at another hospital, the study staff will call them every 3 months for up to 2 years after their last dose of study drugs to learn how they are doing. The calls should last about 5 minutes.

This is an investigational study. ISF35 is not FDA approved or commercially available. It is currently being used for research purposes. Pembrolizumab is FDA approved and commercially available for the treatment of melanoma and non-small cell lung cancer (NSCLC). The study doctor can explain how the study drugs are designed to work.

Up to 36 participants will be enrolled in this study. All will take part at MD Anderson.

Dose Escalation and Cohort Expansion of Safety and Tolerability Study of Intratumoral rAd.CD40L (ISF35) in Combination of Systemic Pembrolizumab in Patients With Refractory Metastatic Melanoma

Phase I/II Dose Escalation and Cohort Expansion of Safety and Tolerability Study of Intratumoral rAd.CD40L (ISF35) in Combination of Systemic Pembrolizumab in Patients With Refractory Metastatic Melanoma

MTD defined as the dose with the smallest absolute difference between the estimate of pi and the true pT for which Prob (pi \> pT \| data) is less than 5%.

Tumor response to therapy assessed using immune-related response criteria (irRC), which is a modified version of the World Health Organization (WHO) criteria.

M.D. Anderson Cancer Center

Infections

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Adenoviridae Infections

Lymphoma, Non-Hodgkin

Lymphoma, B-Cell

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Ad-ISF35, intranodal injection, 3.3 x 10\^10 ISF35 viral particles, every 2-4 weeks up to six total injections.

Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10\^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.

Januario Castro, M.D.

Thomas J Kipps, M.D., Ph.D.

This is a Phase II, open label, fixed dose, repeat injection, single institution study. Eligible subjects will receive up to six doses of Ad-ISF35 injected directly into a selected lymph node under ultrasound guidance. The primary goal is to determine and monitor clinical and biological responses in patients treated with repeat intranodal injections of Ad-ISF35.

This is a phase II clinical trial in which study subjects will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10\^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.

This will be the first time that repeat administration of Ad-ISF35 will be performed via intranodal injection in subjects with a diagnosis other than CLL/SLL. Therefore, in order to allow sufficient time to evaluate the safety and toxicity of this procedure in non-CLL/SLL patients, we will treat the first three non-CLL/SLL subjects with inpatient admission for 24 hours observation at the GCRC-UCSD. If no serious adverse events are observed in these first three patients after they have received their first two injections of ISF35 and have been observed for at least 28 days, then we will proceed with enrollment of cohorts of four subjects per month. This will be done at one week intervals until study enrollment is completed. These subjects will be treated as outpatients at the GCRC and observed for 3 hours prior to discharge.

All subjects with a diagnosis of CLL or SLL will be treated as outpatients at the GCRC and observed for 3 hours prior to discharge. These subjects will not need to be treated in an inpatient setting, based on our previous clinical experience with subjects enrolled on the phase II study of repeat intranodal injections of Ad-ISF35 in CLL/SLL

ISF35 has already been used in Phase I clinical trials. The trials demonstrated that ISF35 treatment is well-tolerated and patients did not experience any significant or unexpected adverse events. Patients reported flu-like symptoms from ISF35, which disappeared within one to three days.

ISF35 is an abbreviation for Immune Stimulatory Factor 35, an offspring of technology discovered by Dr. Thomas J. Kipps, MD, PhD, Professor, Department of Medicine and Deputy Director for Research,UCSD Moores Cancer Center.

Study of Repeat Intranodal Injections of Ad-ISF35

A Phase II Study of Repeat Intranodal Injections of Adenovirus-CD154 (Ad-ISF35) in Patients With Non-Hodgkin's Lymphoma (Follicular, Diffuse Large Cell, Mantle Cell and Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia)

Associate Clinical Professor

Ad-ISF35, intranodal injection, 3.3 x 10\^10 ISF35 viral particles, every 2-4 weeks up to six total injections.

ISF35: Subjects participating in this study will be treated with multiple doses of Ad-ISF35 given via intranodal injection using a fixed dose of 3.3 x 10\^10 ISF35 viral particles. Intranodal injections will be administered every 2-4 weeks up to six total injections.

Ad-ISF35

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Januario E Castro, MD

The study was not completed due to unavailability of the study drug, and therefore data were not collected for this Outcome Measure

Overall Response Rate

Overall Study

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Subjects participating in this study will receive a course of three infusions of 3x10\^8 ISF35-transduced cells at periods of not less than 14 days apart followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) at monthly intervals.

Januario Castro, MD

The study is a Phase 1b open label, non-randomized, single institution clinical trial that is designed to evaluate the safety and tolerability of three repeat infusions of ISF35 followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) in subjects with refractory, resistant, and/or 17p- CLL.

ISF35 has already been used in two Phase I clinical trials. The trials demonstrated that ISF35 treatment is well tolerated and patients did not experience any significant or unexpected adverse events. Patients reported flu-like symptoms from ISF35, which disappeared within one to three days.

The trials also showed that ISF35 stimulates the immune system to act against CLL cells and sensitize leukemic cells to subsequent treatment. Repeat infusions of ISF35 administered as a single agent to subjects with CLL resulted in durable reductions in circulating and lymph-node bound leukemic cells. Furthermore, CLL patients with 17p deletion responded to standard courses of FCR after receiving ISF35 and achieved durable remissions.

ISF35 is an abbreviation for Immune Stimulatory Factor 35, an offspring of technology discovered by Dr. Thomas J. Kipps, MD, PhD, Professor, Department of Medicine and Deputy Director for Research,UCSD Moores Cancer Center.

A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL

A Phase 1b Study of Repeated Doses of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35) in Combination With Fludarabine, Cyclophosphamide and Rituximab (FCR) in Subjects With Chronic Lymphocytic Leukemia (CLL)

The Leukemia and Lymphoma Society

University of California, San Diego

Subjects participating in this study will receive up to two doses of 1x10\^8, 3x10\^8, or 1x10\^9 autologous Ad-ISF35-transduced CLL B cells, depending on the dose they received in the previous Phase I trial.

The study is a Phase Ib extension trial that will assess the toxicity, tolerability, and safety of up to two repeated administrations of 1x10\^8, 3x10\^8, or 1x10\^9 autologous Ad-ISF35-transduced CLL B cells given intravenously to patients with CLL who tolerated ISF35 in the prior Phase I infusion trial at M.D. Anderson.

In a previous Phase I clinical trial at M.D. Anderson, patients with CLL received an intravenous infusion of autologous leukemia cells transduced ex vivo with an adenovirus encoding the wild-type murine CD154. This treatment was well tolerated and without dose-limiting toxicity. Patients each experienced acute reductions in the leukemia-cell blood count and in the size of enlarged lymph nodes and spleen.

The infusion induced changes in circulating bystander, non-infected CLL cells and both acute and long-term clinical responses. The changes in bystander CLL cells were similar to those observed in CLL cells following ligation of CD40, which included enhanced or de novo expression of CD54, CD80, and CD86, allowing the modified CLL cells to function more effectively in presenting antigens to autologous T cells. Following CD40 ligation, CLL cells are induced to express CD95 and DR5 and to undergo changes in expression of pro- and anti-apoptotic proteins, ultimately favoring apoptosis in the CLL cells.

To build upon these results, an extension to this trial will be completed in order to assess the tolerability of repeated infusions of ISF35 and to test whether additional administrations will enhance the anti-leukemic activity exhibited in the previous Phase I trial.

A Phase I Extension Trial of Repeated Infusions of ISF35

A Phase 1B Extension Trial to Allow Repeat Dosing of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35) in Subjects Previously Treated in MDACC Protocol 2004-0914

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)	NCT00779883	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.
A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)	NCT00779883	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.
Dose Escalation and Cohort Expansion of Safety and Tolerability Study of Intratumoral rAd.CD40L (ISF35) in Combination of Systemic Pembrolizumab in Patients With Refractory Metastatic Melanoma	NCT02719015	Melanoma	rAd.CD40L Pembrolizumab	18 Years -	M.D. Anderson Cancer Center
Study of Repeat Intranodal Injections of Ad-ISF35	NCT00942409	Non-Hodgkin's L... Follicular Lymp... Diffuse Large C... Mantle Cell Lym... Small Lymphocyt... Chronic Lymphoc...	ISF35	18 Years -	University of California, San Diego
A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL	NCT00772486	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.
A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL	NCT00772486	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.
A Phase I Extension Trial of Repeated Infusions of ISF35	NCT00783588	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.

Spots Global Cancer Trial Database for isf35

Every month we try and update this database with for isf35 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 isf35

Every month we try and update this database with for isf35 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 isf35 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.