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.

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Chronic Myeloid Leukemia; Hematologic Malignancy; Myeloproliferative Neoplasm
• Intervention / Treatment: Biological: CLL1-CD33 cCAR T cells

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Chengdu, China
    • Recruiting
    • The General Hospital of Western Theater Command
  • Shenzhen, China
    • Not yet recruiting
    • Peking University Shenzhen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLL1-CD33 cCAR T cells; CLL1-CD33cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 and CD33 CARs	Biological: CLL1-CD33 cCAR T cells; CLL1-CD33 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CLL1 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	28 days
Type of dose-limiting toxicity (DLT)	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	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		1 year
Progression-free survival (PFS)		1 year
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

Collaborators and Investigators

• Sponsor: iCell Gene Therapeutics
• Collaborators: The General Hospital of Western Theater Command; Peking University Shenzhen Hospital; iCAR Bio Therapeutics Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: January 2, 2019
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (Actual): January 8, 2019

Study Record Updates

• Last Update Posted (Actual): May 19, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Leukemia; Hematologic Malignancies; CLL1; CD33; CLL1-CD33 cCAR
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Neoplasms; Myelodysplastic Syndromes; Hematologic Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders
• Other Study ID Numbers: ICG141-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No