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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hadassah Medical Organization
Information provided by (Responsible Party):
Immunovative Therapies, Ltd.
ClinicalTrials.gov Identifier:
NCT00558675
First received: November 13, 2007
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

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).


Condition Intervention Phase
Hematological Malignancy
Leukemia
Lymphoma
Multiple Myeloma
Biological: AlloStim
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Immunovative Therapies, Ltd.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Immunological Response [ Time Frame: 30 days, 60 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: December 2009
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Single intravenous infusion of AlloStim
Biological: AlloStim
single intravenous infusion of 1 x 10^9 AlloStim cells
Experimental: 2
Intravenous AlloStim infusion on day 1 and 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
Experimental: 3
Intravenous AlloStim infusion on day 1, 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 and day 14
Experimental: 4
Intravenous AlloStim infusion on day 1, day 7, day 14 and day 21
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558675

Locations
Israel
Hadassah-Hebrew University Medical Center
Jerusalem, Israel, 91120
Sponsors and Collaborators
Immunovative Therapies, Ltd.
Hadassah Medical Organization
Investigators
Principal Investigator: Dr. Michael Har-Noy Immunovative Therapies
  More Information

Additional Information:
Publications:
Responsible Party: Immunovative Therapies, Ltd.
ClinicalTrials.gov Identifier: NCT00558675     History of Changes
Other Study ID Numbers: ITL-001-HMC
Study First Received: November 13, 2007
Last Updated: November 29, 2012
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Immunovative Therapies, Ltd.:
Non-Hodgkins Lymphoma
Hodgkins Lymphoma
Acute Lymphoblastic Leukemia
Chronic Myeloid Leukemia
Chronic Lymphocytic Leukemia
Multiple Myeloma
Immunotherapy
Allogeneic Cell Therapy

Additional relevant MeSH terms:
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Neoplasms by Site

ClinicalTrials.gov processed this record on July 22, 2014