A Phase I/II Study of Mis-Matched Immune Cells (AlloStim) in Patients With Advanced Hematological Malignancy
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
Outcome Measures
Primary Outcome Measures
- Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3 [Within first 48 hours post infusion, at 30 days and at 60 days post infusion]
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 [30 days and 60 days post infusion and yearly thereafter]
- Immunological Response [30 days, 60 days]
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
- Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. Epub 2007 Dec 3.
- Har-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009 Apr;33(4):525-38. doi: 10.1016/j.leukres.2008.08.017. Epub 2008 Oct 1.
- Har-Noy M, Zeira M, Weiss L, Slavin S. Completely mismatched allogeneic CD3/CD28 cross-linked Th1 memory cells elicit anti-leukemia effects in unconditioned hosts without GVHD toxicity. Leuk Res. 2008 Dec;32(12):1903-13. doi: 10.1016/j.leukres.2008.05.007. Epub 2008 Jun 18.
- ITL-001-HMC