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

Immunovative Therapies

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Myeloma; Hematological Malignancy; Lymphoma; Leukemia

Treatments: Biological: AlloStim

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00558675

ITL-001-HMC

Details and patient eligibility

About

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).

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 4 patient groups

1

Experimental group

Description:

Single intravenous infusion of AlloStim

Treatment:

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim

2

Experimental group

Description:

Intravenous AlloStim infusion on day 1 and day 7

Treatment:

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim

3

Experimental group

Description:

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

Treatment:

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim

4

Experimental group

Description:

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

Treatment:

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim

Biological: AlloStim