Clinical trial NCT04156256: CD123-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies
Official title: 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Hematologic Malignancy
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myeloproliferative Neoplasm
Chronic Myeloid Leukemia
Keywords: CD123
CD33
CD123-CD33 cCAR
Leukemia
Hematologic Malignancies
Lead sponsor: iCell Gene Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Peking University Shenzhen Hospital
name: Chengdu Military General Hospital
name: iCAR Bio Therapeutics Ltd.
First posted: 2019-11-07
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. De novo AML
3. Transformed AML
4. MDS with excess blasts (RAEB-2)
5. MDS that is not a candidate for induction chemotherapy.
6. Myeloproliferative neoplasms with blastic transformation
7. Patients have exhausted standard therapeutic options

Exclusion Criteria:

1. Prior solid organ transplantation
2. Potentially curative therapy including hematopoietic cell transplant
3. Prior treatment with CD123xCD3 or CLL1x3 bispecific agents, T cells expressing CD123 CAR or CLL1 CAR, or toxin-conjugated to CD123 or CLL1 antibodies.

Primary outcomes:
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
timeFrame: 28 days
measure: Type of dose-limiting toxicity (DLT)
timeFrame: 28 days
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 1 year
measure: Progression-free survival (PFS)
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Chengdu Military General Hospital
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
Study officials:
affiliation: Peking University Shenzhen Hospital
name: Hongyu Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chengdu Military General Hospital
name: Fang Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: