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

iCell Gene Therapeutics

Status and phase: Unknown; Early Phase 1

Conditions: Hematologic Malignancy; Myeloproliferative Neoplasm; Chronic Myeloid Leukemia; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Treatments: Biological: CD123-CD33 cCAR T cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04156256

ICG136-001

Details and patient eligibility

About

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 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.

Enrollment: 20 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

CD123-CD33 cCAR T cells

Experimental group

Description:

C123-CD33cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CD123 and CD33 CARs

Treatment:

Biological: CD123-CD33 cCAR T cells