Clinical trial NCT00558675: A Phase I/II Study of Mis-Matched Immune Cells (AlloStim) in Patients With Advanced Hematological Malignancy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematological Malignancy
Leukemia
Lymphoma
Multiple Myeloma
Keywords: Non-Hodgkins Lymphoma
Hodgkins Lymphoma
Acute Lymphoblastic Leukemia
Chronic Myeloid Leukemia
Chronic Lymphocytic Leukemia
Multiple Myeloma
Immunotherapy
Allogeneic Cell Therapy
Lead sponsor: Mirror Biologics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hadassah Medical Organization
First posted: 2007-11-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3
timeFrame: Within first 48 hours post infusion, at 30 days and at 60 days post infusion
Secondary outcomes:
measure: Evaluation and reporting of anti-tumor response will be conducted in accordance with internationally accepted criteria for the disease indication being evaluated
timeFrame: 30 days and 60 days post infusion and yearly thereafter
measure: Immunological Response
timeFrame: 30 days, 60 days
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah-Hebrew University Medical Center
Study officials:
affiliation: Immunovative Therapies
name: Dr. Michael Har-Noy
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.