CD123-CD33 cCAR in Patients With Relapsed and/or Refractory, High Risk Hematologic Malignancies

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04156256
• Other study ID #: ICG136-001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 1, 2018
• Est. completion date: September 30, 2020

Study information

• Verified date: January 2019
• Source: iCell Gene Therapeutics
• Contact: Kevin Pinz
• Phone: 6315386218
• Email: kevin.pinz[@]icellgene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 30, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chronic Myeloid Leukemia
• Hematologic Malignancy
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms

Intervention

Biological:
• CD123-CD33 cCAR T cells
CD123-CD33 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CD123 and CD33 CARs.

Locations

Country	Name	City	State
China	Chengdu Military General Hospital	Chengdu
China	Peking University Shenzhen Hospital	Shenzhen

Sponsors (4)

Lead Sponsor	Collaborator
iCell Gene Therapeutics	Chengdu Military General Hospital, iCAR Bio Therapeutics Ltd, Peking University Shenzhen Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		28 days
Primary	Type of dose-limiting toxicity (DLT)		28 days
Primary	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		2 years
Secondary	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	1 year
Secondary	Progression-free survival (PFS)		1 year
Secondary	Overall survival		1 year