A Phase I/II Study of Mis-Matched Immune Cells (AlloStim) in Patients With Advanced Hematological Malignancy

January 17, 2020 updated by: Immunovative Therapies, Ltd.

A Phase I/II Study of Intentionally Mis-Matched, Allogeneic Th1 Memory Cells (AlloStim) Conjugated With CD3/CD28-coated Microbeads in Patients With Relapsed or Refractory Hematological Malignancy

The purpose of this study is to determine the safety and anti-tumor effects of an experimental immunotherapy drug, called AlloStim, which is intentionally mis-matched immune cells which are designed to elicit the same anti-tumor mechanism that occurs in allogeneic bone marrow/stem cell mini-transplant (BMT) procedures, without the toxicity associated with graft vs. host disease (GVHD).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AlloStim is combination biological drug and medical device formulation consisting of allogeneic immune cells that have been expanded and differentiated ex-vivo. These cells are conjugated to monoclonal antibody coated microparticles prior to infusion. The immune cells are living CD4+ memory Th1-like T-cells (T-Stim) that are differentiated from precursors purified from normal donor blood. AlloStim is a composition of T-Stim cells conjugated to paramagnetic epoxy covered microparticles (4.5micron) with covalently bound anti-CD3/anti-CD28 monoclonal antibodies (Dynabeads® ClinExVivo™ CD3/CD28) at a 2:1 bead:cell ratio. The T-Stim cells are intentionally mismatched to the recipient.

The graft vs. tumor (GVT) effect that occurs after allogeneic bone marrow transplant (BMT) is a curative therapy for advanced hematological malignancy but the clinical application of GVT is severely limited by graft vs. host disease (GVHD) toxicity. AlloStim is designed to elicit the "mirror" of the GVT/GVHD effects in the host immune system. Rather than trying to separate these effects, we have proposed that the effects could remain associated and "mirrored" onto the host immune system creating linked host vs. tumor (HVT) and host vs. graft (HVG) effects. We hypothesized that allogeneic Th1 memory cells activated at time of infusion to produce type 1 cytokines and express CD40L would elicit HVT/HVG "mirror effects" in immunocompetent cancer patients.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • 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

  • Israel
      • Jerusalem, Israel, 91120
        • Hadassah-Hebrew University Medical 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:

  • histologically confirmed hematological malignancy
  • unresponsive to chemotherapy and/or recurrence after autologous transplant
  • adequate kidney, liver, lung and heart function

Exclusion Criteria:

  • prior allogeneic transplant
  • immunosuppressive therapy for concurrent medical condition
  • active viral infection

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)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Single intravenous infusion of AlloStim
Biological: AlloStim
single intravenous infusion of 1 x 10^9 AlloStim cells
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7 and day 14
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7, day 14 and day 21
Experimental: 2
Intravenous AlloStim infusion on day 1 and day 7
Biological: AlloStim
single intravenous infusion of 1 x 10^9 AlloStim cells
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7 and day 14
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7, day 14 and day 21
Experimental: 3
Intravenous AlloStim infusion on day 1, day 7 and day 14
Biological: AlloStim
single intravenous infusion of 1 x 10^9 AlloStim cells
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7 and day 14
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7, day 14 and day 21
Experimental: 4
Intravenous AlloStim infusion on day 1, day 7, day 14 and day 21
Biological: AlloStim
single intravenous infusion of 1 x 10^9 AlloStim cells
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7 and day 14
Biological: AlloStim
Intravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7, day 14 and day 21

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3
Time Frame: Within first 48 hours post infusion, at 30 days and at 60 days post infusion
Within first 48 hours post infusion, at 30 days and at 60 days post infusion

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluation and reporting of anti-tumor response will be conducted in accordance with internationally accepted criteria for the disease indication being evaluated
Time Frame: 30 days and 60 days post infusion and yearly thereafter
30 days and 60 days post infusion and yearly thereafter
Immunological Response
Time Frame: 30 days, 60 days
30 days, 60 days

Collaborators and Investigators

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

Sponsor

Immunovative Therapies, Ltd.

Collaborators

Hadassah Medical Organization

Investigators

  • Principal Investigator: Dr. Michael Har-Noy, Immunovative Therapies

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 (Actual)

December 1, 2010

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

November 13, 2007

First Submitted That Met QC Criteria

November 13, 2007

First Posted (Estimate)

November 15, 2007

Study Record Updates

Last Update Posted (Actual)

January 22, 2020

Last Update Submitted That Met QC Criteria

January 17, 2020

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ITL-001-HMC

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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