A Phase I Extension Trial of Repeated Infusions of ISF35

October 30, 2008 updated by: Memgen, LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Subjects must have been enrolled and tolerated the single dose ISF35 in MDACC Protocol 2004-0914.
  2. Subjects must have adequate Ad-ISF35 transduced CLL B cells to allow for at least one additional treatment.
  3. Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study. Both men and women participants must agree to use contraception for the duration of the study.
  4. Subjects must have Zubrod performance status of ≤ 2.

  5. Subjects must have adequate hematologic, renal, hepatic, and coagulation function:

    • Adequate hematologic function:

      • Platelet count ≥ 50,000/μl; AND
      • Hemoglobin ≥ 10 g/dl (may be supported by erythropoietin or transfusion).

    • Adequate renal function:

      • Serum creatinine ≤ 1.5 times upper limit of normal; OR
      • Measured creatinine clearance ≥ 40 mL/min/1.73 m^2.

    • Adequate hepatic function:

      • Total bilirubin ≤ 2.5 times upper limit of normal; AND
      • ALT ≤ 2.5 times upper limit of normal; AND

    • Adequate coagulation tests:

      • Prothrombin time international normalized ratio (INR) ≤ 2; AND
      • Partial thromboplastin time ≤ 1.66 times upper limit of normal
  6. Subjects must give written informed consent for the Phase 1B extension trial.

Exclusion Criteria:

  1. Unresolved toxicity (Grade ≥ 2) from single administration of Add-ISF35 transduced autologous CLL B cells.
  2. Presence of more than 55% prolymphocytes.
  3. Chemotherapy (e.g., purine analogues, alkylating agents, or corticosteroids), antibody therapy, immunotherapy, radiation therapy, or participation in any investigational drug treatment within 4 weeks of enrollment into protocol or at any time during the study.
  4. Ongoing toxicity from prior anti-neoplastic therapy.
  5. Prior gene therapy (EXCEPT Ad-ISF35) or allogeneic stem cell transplantation.
  6. Untreated autoimmune hemolytic anemia or immune thrombocytopenia.
  7. Active infection requiring parenteral antibiotics.
  8. HIV/HBV/HCV seropositivity.
  9. Uncompensated hypothyroidism (defined as TSH greater than 4x upper limit of normal not treated with replacement hormone).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Assess the toxicity, tolerability, and safety of the repeat administration of 1x10^8, 3x10^8, or 1x10^9 autologous Ad-ISF35-transduced CLL B cells in up to 9 patients with CLL who tolerated previous treatment in MDACC Protocol 2004-0914.
Time Frame: Duration of the trial
Duration of the trial

Secondary Outcome Measures

Outcome Measure
Time Frame
Assess pharmacodynamic endpoints including induction of T cell anti-leukemia immune responses, antibody production against autologous CLL B cells, and changes in bystander leukemia cell phenotype.
Time Frame: Two months
Two months
Assess the anti-leukemia activity of the repeat administration of Ad-ISF35 transduced CLL B cells by evaluating reduction in leukemia count, reduction in adenopathy and splenomegaly, and improvement in bone marrow function.
Time Frame: Duration of the trial
Duration of the trial
Assess the quality of life with repeat Ad-ISF35 treatment.
Time Frame: Two months
Two months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memgen, LLC

Investigators

  • Principal Investigator: William G. Wierda, M.D., Ph.D., M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

October 30, 2008

First Submitted That Met QC Criteria

October 30, 2008

First Posted (Estimate)

October 31, 2008

Study Record Updates

Last Update Posted (Estimate)

October 31, 2008

Last Update Submitted That Met QC Criteria

October 30, 2008

Last Verified

October 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL-35-102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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