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

October 23, 2008 updated by: Memgen, LLC
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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

9

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 a diagnosis of B cell CLL, measurable disease, and an

    NCI-WG indication for treatment with one of the following:

    • Massive (>6 cm below left costal margin) or progressive splenomegaly;
    • Massive (>10 cm longest diameter) lymph nodes, nodal clusters, or progressive lymphadenopathy;
    • Progressive anemia;
    • Progressive thrombocytopenia;
    • Weight loss > 10% body weight over the preceding 6 month period;
    • Fatigue attributable to CLL;
    • Fever or night sweats without evidence of infection;
    • Progressive lymphocytosis.
  2. Subjects must be age 18 years or older.
  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 (Appendix B).

  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 be able to give written informed consent.

Exclusion Criteria:

  1. Presence of more than 55% prolymphocytes.
  2. 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.
  3. Ongoing toxicity from prior anti-neoplastic therapy.
  4. Prior gene therapy or allogeneic stem cell transplantation.
  5. Untreated autoimmune hemolytic anemia or immune thrombocytopenia.
  6. Active infection requiring parenteral antibiotics.
  7. Known HIV/HBV/HCV seropositivity.
  8. 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 1x10^8, 3x10^8, and 1x10^9 autologous Ad-ISF35-transduced CLL B cells given as a single intravenous infusion in patients with CLL.
Time Frame: Duration of the trial
Duration of the trial

Secondary Outcome Measures

Outcome Measure
Time Frame
Assess the anti-leukemia activity of a single intravenous dose by evaluating reduction in leukemia count, reduction in adenopathy and splenomegaly, and improvement in bone function.
Time Frame: Duration of the trial
Duration of the trial
Assess the quality of life with ISF35 treatment.
Time Frame: Two months
Two months
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

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

June 1, 2006

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

October 23, 2008

First Submitted That Met QC Criteria

October 23, 2008

First Posted (Estimate)

October 24, 2008

Study Record Updates

Last Update Posted (Estimate)

October 24, 2008

Last Update Submitted That Met QC Criteria

October 23, 2008

Last Verified

October 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL-35-101

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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