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

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.
A Phase I Extension Trial of Repeated Infusions of ISF35	NCT00783588	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.

Spots Global Cancer Trial Database for active immune therapy