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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00558675
• Other study ID #: ITL-001-HMC
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2010
• Est. completion date: March 2013

Study information

• Verified date: November 2012
• Source: Immunovative Therapies, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematological Malignancy
• Leukemia
• Lymphoma
• Multiple Myeloma
• Neoplasms

Intervention

Biological:
• AlloStim
single intravenous infusion of 1 x 10^9 AlloStim cells
• 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
• 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
• 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

Locations

Country	Name	City	State
Israel	Hadassah-Hebrew University Medical Center	Jerusalem

Sponsors (2)

Lead Sponsor	Collaborator
Immunovative Therapies, Ltd.	Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Immunological Response		30 days, 60 days

External Links

•   Immunovative Therapies. Ltd