- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04156256
CD123-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 CD123-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies
Study Overview
Status
Conditions
Intervention / Treatment
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 CD123 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 CD123 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.
CD123-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 Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
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Chengdu, China
- Recruiting
- Chengdu Military General Hospital
-
Shenzhen, China
- Recruiting
- Peking University Shenzhen Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: CD123-CD33 cCAR T cells
C123-CD33cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CD123 and CD33 CARs
|
CD123-CD33 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CD123 and CD33 CARs.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
28 days
|
Type of dose-limiting toxicity (DLT)
Time Frame: 28 days
|
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
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 1 year
|
1 year
|
|
Progression-free survival (PFS)
Time Frame: 1 year
|
1 year
|
|
Overall Response Rate (ORR)
Time Frame: 1 year
|
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
|
1 year
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ICG136-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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