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

Phase 1

Completed

• Conditions: Lymphoma; Leukemia; Hematological Malignancy; Multiple Myeloma
• Interventions: Biological: AlloStim

• Registration Number: NCT00558675
• Lead Sponsor: Mirror Biologics, Inc.

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.

Study Timeline

• Study First Submitted: 2007-11-13
• Study First Submitted QC: 2007-11-13
• Study First Posted: 2007-11-15
• Study Start: 2010-12
• Status Verified: 2012-11
• Primary Completion: 2012-12
• Study Completion: 2013-03
• Last Update Submitted: 2020-01-17
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• histologically confirmed hematological malignancy
• unresponsive to chemotherapy and/or recurrence after autologous transplant
• adequate kidney, liver, lung and heart function

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Exclusion Criteria

• prior allogeneic transplant
• immunosuppressive therapy for concurrent medical condition
• active viral infection

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
3	AlloStim	Intravenous AlloStim infusion on day 1, day 7 and day 14
2	AlloStim	Intravenous AlloStim infusion on day 1 and day 7
4	AlloStim	Intravenous AlloStim infusion on day 1, day 7, day 14 and day 21
1	AlloStim	Single intravenous infusion of AlloStim

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Hadassah-Hebrew University Medical Center; 🇮🇱 Jerusalem, Israel