Hematological Malignancy, Leukemia, Lymphoma, Multiple Myeloma
Conditions
Keywords
Non-Hodgkins Lymphoma, Hodgkins Lymphoma, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia, Multiple Myeloma, Immunotherapy, Allogeneic Cell Therapy
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.
Interventions
BIOLOGICALAlloStim
single intravenous infusion of 1 x 10\^9 AlloStim cells
Sponsors
Hadassah Medical Organization
Mirror Biologics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Israel
Outcome results
None listed