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

Sponsor
iCell Gene Therapeutics (Industry)
Overall Status
Unknown status
CT.gov ID
NCT04156256
Collaborator
Peking University Shenzhen Hospital (Other), Chengdu Military General Hospital (Other), iCAR Bio Therapeutics Ltd. (Industry)
20
2
1
31
10
0.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: CD123-CD33 cCAR T cells
Early Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 1, 2018
Anticipated Primary Completion Date :
Sep 30, 2020
Anticipated Study Completion Date :
Sep 30, 2020

Arms and Interventions

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

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.

Outcome Measures

Primary Outcome Measures

  1. 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]

  2. Type of dose-limiting toxicity (DLT) [28 days]

  3. 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

  1. Overall Response Rate (ORR) [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

  2. Progression-free survival (PFS) [1 year]

  3. Overall survival [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Chengdu Military General Hospital Chengdu China
2 Peking University Shenzhen Hospital Shenzhen China

Sponsors and Collaborators

  • iCell Gene Therapeutics
  • Peking University Shenzhen Hospital
  • Chengdu Military General Hospital
  • iCAR Bio Therapeutics Ltd.

Investigators

  • Principal Investigator: Hongyu Zhang, MD, PhD, Peking University Shenzhen Hospital
  • Principal Investigator: Fang Liu, MD, PhD, Chengdu Military General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
iCell Gene Therapeutics
ClinicalTrials.gov Identifier:
NCT04156256
Other Study ID Numbers:
  • ICG136-001
First Posted:
Nov 7, 2019
Last Update Posted:
Nov 12, 2019
Last Verified:
Jan 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by iCell Gene Therapeutics
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 12, 2019