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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hematological Malignancy, Leukemia, Lymphoma, Multiple Myeloma

Intervention / Treatment
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* Biological: AlloStim
* Biological: AlloStim
* Biological: AlloStim
* Biological: AlloStim


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Single intravenous infusion of AlloStim | Biological: AlloStim<br>* single intravenous infusion of 1 x 10^9 AlloStim cells<br>|
| Experimental: 2<br>Intravenous AlloStim infusion on day 1 and day 7 | Biological: AlloStim<br>* 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<br>|
| Experimental: 3<br>Intravenous AlloStim infusion on day 1, day 7 and day 14 | Biological: AlloStim<br>* 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<br>|
| Experimental: 4<br>Intravenous AlloStim infusion on day 1, day 7, day 14 and day 21 | Biological: AlloStim<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkins Lymphoma, Hodgkins Lymphoma, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia, Multiple Myeloma, Immunotherapy, Allogeneic Cell Therapy