Hematologic MalignancyEarly Phase 1NCT03795779
CLL1-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies
A Early Phase 1 study testing CLL1-CD33 cCAR T cells in people with Hematologic Malignancy and Acute Myeloid Leukemia, run by iCell Gene Therapeutics at 2 sites in China.
Trial summary
Phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CLL1-CD33 cCAR in patients with relapsed and/or refractory, high risk hematologic malignancies. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hematologic Malignancy, Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- CLL1-CD33 cCAR T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesChina
- Study dates
- 1 Mar 2018to 30 Sep 2022
- Phase
- Early Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Prior HSCT relapse beyond 6 months without active GVHD; systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks
- De novo AML
- Transformed AML
- MDS with excess blasts (RAEB-2)
- MDS that is not a candidate for induction chemotherapy.
- Myeloproliferative neoplasms with blastic transformation
- Patients have exhausted standard therapeutic options
Who cannot join
- Prior solid organ transplantation
- Potentially curative therapy including hematopoietic cell transplant
- Prior treatment with CD123xCD3 or CLL1x3 bispecific agents, T cells expressing CD123 CAR or CLL1 CAR, or toxin-conjugated to CD123 or CLL1 antibodies.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
The General Hospital of Western Theater Command
Chengdu
Fang Liu, MD, PhD
lfyh2006@yahoo.com
- Not yet recruiting
Peking University Shenzhen Hospital
Shenzhen
Hongyu Zhang, MD, PhD
HongyuZhang@pkuszh.com
About this study
Official title: Phase I, Interventional, Single Arm, Open Label, Treatment Study to Evaluate The Safety and Tolerability of CLL1-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies.
Phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CLL1-CD33 cCAR in patients with relapsed and/or refractory, high risk hematologic malignancies.
Read the detailed description
AML bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CLL1 expression comprise a rare population that also plays an important role in disease progression and relapse for myeloid malignancies. CD33 is widely expressed in AML, high risk myelodysplastic syndromes (MDS) and myeloproliferative neoplasms. Targeting both CD33 and CLL1 surface antigens together may offer two distinct benefits. First, targeting both bulk disease and leukemic stem cells together allows for a more comprehensive ablation of the disease. Second, dual targeting of myeloid malignancies by both CD33 and CLL1 directed therapy overcomes the pitfalls of single-antigen therapy by preventing relapse due to antigen loss. While loss of a single antigen under antigen-specific selection pressure is possible, loss of two antigens simultaneously is much less likely.
CLL1-CD33 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. cCAR intends to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.
- Conditions
- Hematologic Malignancy, Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Chronic Myeloid Leukemia
- Being tested
- CLL1-CD33 cCAR T cells
- Keywords
- CLL1, CD33, CLL1-CD33 cCAR, Leukemia, Hematologic Malignancies
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myeloproliferative Disorders, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLL1-CD33 cCAR T cellsBiological
CLL1-CD33 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs.
| Study group | Role | What they receive |
|---|---|---|
| CLL1-CD33 cCAR T cells | Experimental | CLL1-CD33cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs Receives: Biological: CLL1-CD33 cCAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with dose limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: 28 days
Type of dose-limiting toxicity (DLT)
Measured: 28 days
Number of participants with adverse event by severity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: 2 years
Secondary outcomes (3)
Overall Response Rate (ORR)
Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CR1), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies
Measured: 1 year
Progression-free survival (PFS)
Measured: 1 year
Overall survival
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2019
- Study start1 Mar 2018
- Primary completion30 Sep 2022 (estimated)
- Study completion30 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- iCell Gene Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The General Hospital of Western Theater Command, iCAR Bio Therapeutics Ltd., Peking University Shenzhen Hospital
- Responsible party
- Sponsor
- Investigators
- Hongyu Zhang, MD, PhD, Principal investigator, Peking University Shenzhen HospitalFang Liu, MD, PhD, Principal investigator, The General Hospital of Western Theater Command
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03795779
- Sponsor's protocol ID
- ICG141-001
- Status last verified
- May 2021
- First submitted
- 2 Jan 2019
- Last updated
- 19 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Interventional, Single Arm, Open Label, Treatment Study to Evaluate The Safety and Tolerability of CLL1-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies.
- ClinicalTrials.gov ID
- NCT03795779
- Acronym / sponsor ID
- ICG141-001
- Conditions
- Hematologic Malignancy, Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Chronic Myeloid Leukemia
- Keywords
- CLL1, CD33, CLL1-CD33 cCAR, Leukemia, Hematologic Malignancies
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- iCell Gene TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- The General Hospital of Western Theater Command, iCAR Bio Therapeutics Ltd., Peking University Shenzhen Hospital
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 30 Sep 2022 (estimated)
- Study completion
- 30 Sep 2022 (estimated)
- First posted
- 8 Jan 2019 (actual)
- 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.
Phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CLL1-CD33 cCAR in patients with relapsed and/or refractory, high risk hematologic malignancies.
Detailed description
AML bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CLL1 expression comprise a rare population that also plays an important role in disease progression and relapse for myeloid malignancies. CD33 is widely expressed in AML, high risk myelodysplastic syndromes (MDS) and myeloproliferative neoplasms. Targeting both CD33 and CLL1 surface antigens together may offer two distinct benefits. First, targeting both bulk disease and leukemic stem cells together allows for a more comprehensive ablation of the disease. Second, dual targeting of myeloid malignancies by both CD33 and CLL1 directed therapy overcomes the pitfalls of single-antigen therapy by preventing relapse due to antigen loss. While loss of a single antigen under antigen-specific selection pressure is possible, loss of two antigens simultaneously is much less likely.
CLL1-CD33 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. cCAR intends to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CLL1-CD33 cCAR T cells | Experimental | Biological: CLL1-CD33 cCAR T cellsCLL1-CD33cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Prior HSCT relapse beyond 6 months without active GVHD; systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks
- De novo AML
- Transformed AML
- MDS with excess blasts (RAEB-2)
- MDS that is not a candidate for induction chemotherapy.
Key exclusion criteria (3 listed)
- Prior solid organ transplantation
- Potentially curative therapy including hematopoietic cell transplant
- Prior treatment with CD123xCD3 or CLL1x3 bispecific agents, T cells expressing CD123 CAR or CLL1 CAR, or toxin-conjugated to CD123 or CLL1 antibodies.
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 |
|---|---|---|
| CLL1-CD33 cCAR T cellsCLL1-CD33 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs. | Biological | CLL1-CD33 cCAR T cells |
Primary outcome
Number of participants with dose limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: 28 days
Type of dose-limiting toxicity (DLT)
Time frame: 28 days
Number of participants with adverse event by severity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: 2 years
3 secondary outcomes
Overall Response Rate (ORR)
Time frame: 1 year
Progression-free survival (PFS)
Time frame: 1 year
Overall survival
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- Individual participant dataSharing planned: No
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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.
Hongyu Zhang, MD, PhD principal investigator
Peking University Shenzhen Hospital
Fang Liu, MD, PhD principal investigator
The General Hospital of Western Theater Command
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing CLL1-CD33 cCAR T cells in people with Hematologic Malignancy and Acute Myeloid Leukemia, run by iCell Gene Therapeutics at 2 sites in China.
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 7 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: status not confirmed, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kevin Pinz (6315386218, kevin.pinz@icellgene.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with dose limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 May 2021.