Hematological MalignancyPhase 1/2NCT00558675
A Phase I/II Study of Mis-Matched Immune Cells (AlloStim) in Patients With Advanced Hematological Malignancy
A Phase 1/2 study testing AlloStim in people with Hematological Malignancy and Leukemia, run by Mirror Biologics, Inc. at 1 site in Israel.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancy, Leukemia, Lymphoma
- What is being tested?
- AlloStim
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2010to Mar 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histologically confirmed hematological malignancy
- unresponsive to chemotherapy and/or recurrence after autologous transplant
- adequate kidney, liver, lung and heart function
Who cannot join
- prior allogeneic transplant
- immunosuppressive therapy for concurrent medical condition
- active viral infection
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Conditions
- Hematological Malignancy, Leukemia, Lymphoma, Multiple Myeloma
- Being tested
- AlloStim
- Keywords
- Non-Hodgkins Lymphoma, Hodgkins Lymphoma, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia, Multiple Myeloma, Immunotherapy, Allogeneic Cell Therapy
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Lymphoma, Multiple Myeloma, Lymphoma, Non-Hodgkin, Hodgkin Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlloStimBiological
single intravenous infusion of 1 x 10^9 AlloStim cells
AlloStimBiological
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
AlloStimBiological
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
AlloStimBiological
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Single intravenous infusion of AlloStim Receives: Biological: AlloStim |
| 2 | Experimental | Intravenous AlloStim infusion on day 1 and day 7 Receives: Biological: AlloStim |
| 3 | Experimental | Intravenous AlloStim infusion on day 1, day 7 and day 14 Receives: Biological: AlloStim |
| 4 | Experimental | Intravenous AlloStim infusion on day 1, day 7, day 14 and day 21 Receives: Biological: AlloStim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3
Measured: Within first 48 hours post infusion, at 30 days and at 60 days post infusion
Secondary outcomes (2)
Evaluation and reporting of anti-tumor response will be conducted in accordance with internationally accepted criteria for the disease indication being evaluated
Measured: 30 days and 60 days post infusion and yearly thereafter
Immunological Response
Measured: 30 days, 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2007 (estimated)
- Study startDec 2010
- Primary completionDec 2012
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hematological MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirror Biologics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Responsible party
- Sponsor
- Investigators
- Dr. Michael Har-Noy, Principal investigator, Immunovative Therapies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00558675
- Sponsor's protocol ID
- ITL-001-HMC
- Status last verified
- Nov 2012
- First submitted
- 13 Nov 2007
- Last updated
- 22 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18054441Har-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.
PubMed 18565579Har-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.
PubMed 18834631
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00558675
- Acronym / sponsor ID
- ITL-001-HMC
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Mirror Biologics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Study start
- Dec 2010 (actual)
- Primary completion
- Dec 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 15 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: AlloStimSingle intravenous infusion of AlloStim |
| 2 | Experimental | Biological: AlloStimIntravenous AlloStim infusion on day 1 and day 7 |
| 3 | Experimental | Biological: AlloStimIntravenous AlloStim infusion on day 1, day 7 and day 14 |
| 4 | Experimental | Biological: AlloStimIntravenous AlloStim infusion on day 1, day 7, day 14 and day 21 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- histologically confirmed hematological malignancy
- unresponsive to chemotherapy and/or recurrence after autologous transplant
- adequate kidney, liver, lung and heart function
Key exclusion criteria (3 listed)
- prior allogeneic transplant
- immunosuppressive therapy for concurrent medical condition
- active viral infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlloStimsingle intravenous infusion of 1 x 10^9 AlloStim cells | Biological | 1 |
| AlloStimIntravenous infusion of 1 x 10^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10^8 AlloStim on day 7 | Biological | 2 |
| AlloStimIntravenous 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 | Biological | 3 |
| AlloStimIntravenous 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 | Biological | 4 |
Primary outcome
Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3
Time frame: Within first 48 hours post infusion, at 30 days and at 60 days post infusion
2 secondary outcomes
Evaluation and reporting of anti-tumor response will be conducted in accordance with internationally accepted criteria for the disease indication being evaluated
Time frame: 30 days and 60 days post infusion and yearly thereafter
Immunological Response
Time frame: 30 days, 60 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
- Background: PubMed 18054441Har-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.
- Background: PubMed 18565579Har-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.
- Background: PubMed 18834631Har-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Michael Har-Noy principal investigator
Immunovative Therapies
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AlloStim in people with Hematological Malignancy and Leukemia, run by Mirror Biologics, Inc. at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3 (time frame: Within first 48 hours post infusion, at 30 days and at 60 days post infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00558675, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.