Solid Tumors Stage II, Stage III and Stage IVPhase 1/2NCT01065441
Experimental Therapeutic Cancer Vaccine Created In-situ in Patients With Stage II-Stage IV Cancer
A Phase 1/2 study testing AlloStim and Cryoablation in people with Solid Tumors Stage II, Stage III and Stage IV and Breast Cancer, run by Michael Har-Noy at 1 site in Israel.
Trial summary
A Phase I/II study of an in-situ therapeutic cancer vaccine. Vaccines contain a source of antigen and and adjuvant. In this study the source of tumor antigen comes from the killing of a selected tumor by cryoablation (killing using extreme cold) and the adjuvant is intentionally mis-matched immune cells (AlloStim-TM)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors Stage II, Stage III and Stage IV, Breast Cancer, Colorectal Cancer
- What is being tested?
- AlloStim and Cryoablation
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 9 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2010to Jul 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
- 18 years or older
- Stage II-IV including breast cancer, colorectal cancer, non-small cell lung cancer, ovarian or other gynecological cancer, prostate cancer, pancreatic or other GI cancer, melanoma, head or neck cancer or lymphoma/plasmacytoma.
- Measurable disease determined upon review of abdominal and/or chest CT scan within 60 days of evaluation for study inclusion with a target tumor lesion for cryoablation or alcohol ablation located in liver, kidney, bone, lung, adrenal, pancreas, lymph node, skin, neck or prostate deemed to be accessible for percutaneous access or carcinomatosis or malignant ascites or malignant pleural effusion.
- When applicable, acceptable cryoablation procedure technique risk: the target tumor for ablation must have adequate distance from adjacent vasculature and other organs to permit safe application of cryoprobe (generally, more than a 2.5cm clearance of the cryoprobe from any vital structure such as the bowel, inferior vena cava, or aorta). The safety assessment of the cryoprobe placement will be made an attending radiologist based on imaging studies.
- Life expectancy >90 days
- No bevacizumab (Avastin®) within 6 weeks of planned cryoablation procedure
Show all 24Show fewer
- ECOG status 0-2
- No concurrent medication known to interfere with platelet function or coagulation (e.g., aspirin, ibuprofen, clopidogrel, or warfarin) unless such medications can be discontinued for an appropriate time period based on the drug half-life and known activity (e.g., aspirin for 7 days) prior to cryoablation procedure
- No low molecular weight heparin preparations unless can be discontinued 8 hours prior to cryoablation
- At least 2 weeks since prior cytotoxic chemotherapy
- Absolute granulocyte count ≥ 1,200/mm3
- Platelet count ≥ 100,000/mm3
- PT/INR ≤ 1.5
- o INR correctable to ≤ 1.5 or a PT/PTT correctable to normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be monitored weekly prior to the cryoablation day to assure INR is stable. However, heparin or warfarin must be withheld prior to cryoablation such that the above criteria are met.
- Hemoglobin ≥ 9 g/dL
- Creatinine ≤ 1.5 mg/dL
- Total bilirubin ≤ 1.5 times normal
- Alkaline phosphatase ≤ 2.5 times normal (≤ 5 times normal if liver involvement)
- Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN
- Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN
- Not pregnant or lactating
- Patients with child bearing potential must agree to use adequate contraception
- No psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation
- Study specific informed consent
Who cannot join
- Taking anticoagulant medication for concomitant medical condition (unless can be safely discontinued for cryoablation procedure)
- Prior allogeneic bone marrow/stem cell or solid organ transplant
- Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 30 days of the first day of study drug treatment
- o Topical and inhaled corticosteroids are permitted
- Concomitant active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis)
- Prior experimental cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine)
Show all 15Show fewer
- Immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 3 months of study entry
- History of blood transfusion reactions
- Known allergy to bovine products
- Know allergy to murine products
- Progressive viral or bacterial infection
- o All infections must be resolved and the patient must remain afebrile for seven days without antibiotics prior to being placed on study
- Cardiac disease of symptomatic nature or cardiac ejection fraction < 45%
- Symptomatic pulmonary disease or FEV1, FVC, and DLCO ≤ 50% predicted
- History of HIV positivity or AIDS o HBV and/or HCV positivity is permitted
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Study of an Experimental Therapeutic Cancer Vaccine Created In-situ in Patients With Stage II-Stage IV Cancers
A Phase I/II study of an in-situ therapeutic cancer vaccine. Vaccines contain a source of antigen and and adjuvant. In this study the source of tumor antigen comes from the killing of a selected tumor by cryoablation (killing using extreme cold) and the adjuvant is intentionally mis-matched immune cells (AlloStim-TM) engineered to produce inflammatory cytokines.
Read the detailed description
This is a Phase I/II clinical study to investigate the optimal protocol and indication for creating a personalized anti-tumor vaccine within the body of patients with cancer. The aim of the study is to evaluate the safety of administration and anti-tumor effect of a vaccine protocol that has three separate steps. Cancer patients generally present with an immune response to cancer biased to a Th2 response, while a Th1 response is considered necessary for mediating anti-tumor immunity. The first step of the study consists of multiple intradermal priming doses of AlloStimTM. The aim of this step is to create Th1 immunity to the alloantigens in AlloStimTM, thus increasing the number of Th1 cells in circulation. The second step of the protocol involves the cryoablation of a selected tumor lesion followed by an intratumoral AlloStimTM injection. The aim of this step is to generate tumor-specific CTL killer cells in the circulation. The final step is an intravenous infusion of AlloStimTM. The aim of this step is to activate circulating Th1 cells, killer cells, and natural killer cells. The further aim of this step is to create an inflammatory environment that can break-down the ability of the tumor to avoid an anti-tumor immune response. In patients with partial responses and recurrence of disease, additional intravenous "booster" infusions are utilized to reactivate the circulating immune cells.
- Conditions
- Solid Tumors Stage II, Stage III and Stage IV, Breast Cancer, Colorectal Cancer, Prostate Cancer, Melanoma, Ovarian Cancer
- Being tested
- AlloStim, Cryoablation
- Keywords
- breast cancer, colorectal cancer, prostate cancer, melanoma, ovarian cancer, GI cancer, Sarcoma, Renal Cell Carcinoma
- Medical subject headings
- Breast Neoplasms, Colorectal Neoplasms, Prostatic Neoplasms, Melanoma, Ovarian Neoplasms, Sarcoma, Carcinoma, Non-Small-Cell Lung, Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlloStimBiological
Patients meeting eligibility criteria will be primed with at least three and up to nine intradermal AlloStim-TM injections at a frequency of every 2-8 days at doses between 1-4 x 10^7 cells
CryoablationProcedure or surgery
Percutaneous cryoablation of selected tumor lesion under CT or US guidance
AlloStimBiological
intratumoral injection of AlloStim-TM into cryoablated tumor lesion at a dose of 1-6 x 10^7 cells
AlloStimBiological
intravenous AlloStim-TM at doses between 1 x 10^7 to 1 x 10^9 cells
AlloStimBiological
Intraperitoneal AlloStim-TM infusion in patients with peritoneal carcinomatosis and/or ascites
AlloStimBiological
Patients with malignant pleural effusion may receive intrapleural AlloStim-TM infusion at a dose of 5-10 x 10^7 cells.
AlloStimBiological
Patients with palpable tumors may receive alcohol ablation and intratumoral AlloStim-TM
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the evaluation of any drug-related toxicity associated with AlloStimTM administration as well as the reversibility of such toxicity.
Measured: 90 days
Secondary outcomes (2)
The secondary end-point is the evaluation of the anti-tumor effect of AlloStimTM administration.
Measured: 1 year
The tertiary end-point is the evaluation of the immunological response to AlloStim-TM administration.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2010 (estimated)
- Study startDec 2010
- Primary completionDec 2012
- Study completionJul 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 Solid Tumors Stage II, Stage III and Stage IVStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Har-Noy
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Responsible party
- Sponsor-investigator, Michael Har-Noy, Mirror Biologics, Inc.
- Investigators
- Tamar Peretz, MD, Principal investigator, Hadassah Medical OrganizationDr. Michael Har-Noy, Study chair, Mirror Biologics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01065441
- Sponsor's protocol ID
- ITL-002-HMC
- Status last verified
- Jan 2020
- First submitted
- 7 Feb 2010
- Last updated
- 22 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Har-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 18834631Har-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, 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 18054441
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 an Experimental Therapeutic Cancer Vaccine Created In-situ in Patients With Stage II-Stage IV Cancers
- ClinicalTrials.gov ID
- NCT01065441
- Acronym / sponsor ID
- ITL-002-HMC
- Conditions
- Solid Tumors Stage II, Stage III and Stage IV, Breast Cancer, Colorectal Cancer, Prostate Cancer, Melanoma, Ovarian Cancer
- Keywords
- breast cancer, colorectal cancer, prostate cancer, melanoma, ovarian cancer, GI cancer, Sarcoma, Renal Cell Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Michael Har-NoyIndustry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Study start
- Dec 2010 (actual)
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 9 Feb 2010 (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.
A Phase I/II study of an in-situ therapeutic cancer vaccine. Vaccines contain a source of antigen and and adjuvant. In this study the source of tumor antigen comes from the killing of a selected tumor by cryoablation (killing using extreme cold) and the adjuvant is intentionally mis-matched immune cells (AlloStim-TM) engineered to produce inflammatory cytokines.
Detailed description
This is a Phase I/II clinical study to investigate the optimal protocol and indication for creating a personalized anti-tumor vaccine within the body of patients with cancer. The aim of the study is to evaluate the safety of administration and anti-tumor effect of a vaccine protocol that has three separate steps. Cancer patients generally present with an immune response to cancer biased to a Th2 response, while a Th1 response is considered necessary for mediating anti-tumor immunity. The first step of the study consists of multiple intradermal priming doses of AlloStimTM. The aim of this step is to create Th1 immunity to the alloantigens in AlloStimTM, thus increasing the number of Th1 cells in circulation. The second step of the protocol involves the cryoablation of a selected tumor lesion followed by an intratumoral AlloStimTM injection. The aim of this step is to generate tumor-specific CTL killer cells in the circulation. The final step is an intravenous infusion of AlloStimTM. The aim of this step is to activate circulating Th1 cells, killer cells, and natural killer cells. The further aim of this step is to create an inflammatory environment that can break-down the ability of the tumor to avoid an anti-tumor immune response. In patients with partial responses and recurrence of disease, additional intravenous "booster" infusions are utilized to reactivate the circulating immune cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 18 years or older
- Stage II-IV including breast cancer, colorectal cancer, non-small cell lung cancer, ovarian or other gynecological cancer, prostate cancer, pancreatic or other GI cancer, melanoma, head or neck cancer or lymphoma/plasmacytoma.
- Measurable disease determined upon review of abdominal and/or chest CT scan within 60 days of evaluation for study inclusion with a target tumor lesion for cryoablation or alcohol ablation located in liver, kidney, bone, lung, adrenal, pancreas, lymph node, skin, neck or prostate deemed to be accessible for percutaneous access or carcinomatosis or malignant ascites or malignant pleural effusion.
- When applicable, acceptable cryoablation procedure technique risk: the target tumor for ablation must have adequate distance from adjacent vasculature and other organs to permit safe application of cryoprobe (generally, more than a 2.5cm clearance of the cryoprobe from any vital structure such as the bowel, inferior vena cava, or aorta). The safety assessment of the cryoprobe placement will be made an attending radiologist based on imaging studies.
- Life expectancy >90 days
Key exclusion criteria (15 listed)
- Taking anticoagulant medication for concomitant medical condition (unless can be safely discontinued for cryoablation procedure)
- Prior allogeneic bone marrow/stem cell or solid organ transplant
- Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 30 days of the first day of study drug treatment
- o Topical and inhaled corticosteroids are permitted
- Concomitant active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis)
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 |
|---|---|---|
| AlloStimPatients meeting eligibility criteria will be primed with at least three and up to nine intradermal AlloStim-TM injections at a frequency of every 2-8 days at doses between 1-4 x 10^7 cells | Biological | – |
| CryoablationPercutaneous cryoablation of selected tumor lesion under CT or US guidance | Procedure or surgery | – |
| AlloStimintratumoral injection of AlloStim-TM into cryoablated tumor lesion at a dose of 1-6 x 10^7 cells | Biological | – |
| AlloStimintravenous AlloStim-TM at doses between 1 x 10^7 to 1 x 10^9 cells | Biological | – |
| AlloStimIntraperitoneal AlloStim-TM infusion in patients with peritoneal carcinomatosis and/or ascites | Biological | – |
| AlloStimPatients with malignant pleural effusion may receive intrapleural AlloStim-TM infusion at a dose of 5-10 x 10^7 cells. | Biological | – |
| AlloStimPatients with palpable tumors may receive alcohol ablation and intratumoral AlloStim-TM | Biological | – |
Primary outcome
The primary endpoint is the evaluation of any drug-related toxicity associated with AlloStimTM administration as well as the reversibility of such toxicity.
Time frame: 90 days
2 secondary outcomes
The secondary end-point is the evaluation of the anti-tumor effect of AlloStimTM administration.
Time frame: 1 year
The tertiary end-point is the evaluation of the immunological response to AlloStim-TM administration.
Time frame: 90 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 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.
- 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 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.
Related trials for Solid Tumors Stage II, Stage III and Stage IV
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
RecruitingPhase 2
Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program
Advanced Esophageal Squamous Cell Carcinoma, Advanced Renal Cell Carcinoma
Active, not recruitingPhase 1/2
Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
Locally Advanced Malignant Solid Neoplasm, Locally Advanced Unresectable Cholangiocarcinoma
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.
Tamar Peretz, MD principal investigator
Hadassah Medical Organization
Dr. Michael Har-Noy study chair
Mirror Biologics, Inc.
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 and Cryoablation in people with Solid Tumors Stage II, Stage III and Stage IV and Breast Cancer, run by Michael Har-Noy 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 24 inclusion and 15 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?
The primary endpoint is the evaluation of any drug-related toxicity associated with AlloStimTM administration as well as the reversibility of such toxicity. (time frame: 90 days). 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 NCT01065441, 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.