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

NCT ID: NCT00558675

Last Updated: 2020-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2013-03-31

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).

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.

Conditions

Hematological Malignancy; Leukemia; Lymphoma; Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Single intravenous infusion of AlloStim

Group Type: EXPERIMENTAL

AlloStim

Intervention Type: BIOLOGICAL

single intravenous infusion of 1 x 10\^9 AlloStim cells

2

Intravenous AlloStim infusion on day 1 and day 7

Group Type: EXPERIMENTAL

AlloStim

Intervention Type: BIOLOGICAL

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

3

Intravenous AlloStim infusion on day 1, day 7 and day 14

Group Type: EXPERIMENTAL

AlloStim

Intervention Type: BIOLOGICAL

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

4

Intravenous AlloStim infusion on day 1, day 7, day 14 and day 21

Group Type: EXPERIMENTAL

AlloStim

Intervention Type: BIOLOGICAL

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

Interventions

AlloStim

single intravenous infusion of 1 x 10\^9 AlloStim cells

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: BIOLOGICAL

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: collaborator

Mirror Biologics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr. Michael Har-Noy

Role: PRINCIPAL_INVESTIGATOR

Immunovative Therapies

Locations

Hadassah-Hebrew University Medical Center

Jerusalem, , Israel

Countries

Israel

References

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. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.

Reference Type: BACKGROUND

PMID: 18054441 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18565579 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18834631 (View on PubMed)

Other Identifiers

ITL-001-HMC

Identifier Type: -

Identifier Source: org_study_id