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

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 30, 2020

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.

Interventions

  • 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.

Arms, Groups and Cohorts

  • 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

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • 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
  • Progression-free survival (PFS)
    • Time Frame: 1 year
  • Overall survival
    • Time Frame: 1 year

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • iCell Gene Therapeutics
  • Collaborator
    • Peking University Shenzhen Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Hongyu Zhang, MD, PhD, Principal Investigator, Peking University Shenzhen Hospital
    • Fang Liu, MD, PhD, Principal Investigator, Chengdu Military General Hospital
  • Overall Contact(s)
    • Kevin Pinz, 6315386218, kevin.pinz@icellgene.com

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