Dual CD33-CLL1-CAR-T Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

NCT05016063 | Unknown Early Phase 1

• 1 other identifier: Dual CD33-CLL1 CAR-T cells
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I, interventional, single-arm, open-label, treatment study to evaluate the safety and effectiveness of CD33-CLL1 CAR in patients with relapsed and/or refractory acute myeloid leukemia (AML).

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CRi), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies

  4 weeks after infusion

• the safety evaluation of Dual CD33-CLL1 CAR-T cells

  Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  within 4 weeks after infusion

Secondary Outcomes (2)

• Progression-free survival (PFS)

  up to 2 years after infusion

• Overall survival(OS)

  up to 2 years after infusion

Study Arms (1)

Dual CD33-CLL1 CAR-T cells

EXPERIMENTAL

CD33-CLL1 CAR T cells

Drug: Fludarabine; Drug: Cytoxan; Biological: Dual CD33-CLL1 CAR-T cells

Interventions

Fludarabine DRUG

recommendation: 30mg/m2 (D-5\~D-3),determined by tumor burden at baseline.

Dual CD33-CLL1 CAR-T cells

Cytoxan DRUG

recommendation: 300-500mg/m2 (D-5\~D-3),determined by tumor burden at baseline.

Dual CD33-CLL1 CAR-T cells

Dual CD33-CLL1 CAR-T cells BIOLOGICAL

CD33-CLL1 CAR-T infusion (starting at dose level 1 \[DL1\]: 0.5 x 106 transduced CAR-T cells/kg) on Day 0.

Dual CD33-CLL1 CAR-T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance status score ≤ 2.
• Life expectancy ≥ 12 weeks from the time of enrollment.
• Disease status at the time of enrollment: -Patients with AML (except M3) who have not achieved complete remission after standard chemotherapy regimens; -Not suitable or unconditional for allogeneic hematopoietic stem cell transplantation; -Patients with recurrent acute myeloid leukemia after autologous hematopoietic stem cell transplantation without active graft-versus-host disease (GVHD).
• CD33 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or greater than 80% by flow cytometry.
• Adequate main organ function as assessed by the following laboratory requirements: creatinine ≤ 2.5 × upper limit of normal, cardiac ejection fraction ≥ 40%, oxygen saturation ≥ 90%, total bilirubin ≤ 3 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, Hgb≥80g/L.
• Without history of accepting anti-cancer therapy, including chemotherapy, radiotherapy, immunotherapy (immune suppressive drugs or corticosteroid treatment) within 4 weeks of screening.
• Women of child-bearing age must have evidence of negative pregnancy test.
• Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.
• After discussion by the expert group, the patient's condition was analyzed and combined with the general physical condition of the patient, the benefit of participating in the clinical trial was greater than the risk.
• All participants must have the ability to understand and willingness to sign a written informed consent.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia \[PML\]/retinoic acid receptor \[RAR\] alpha \[a\]) and variants excluded.
• Active acute or chronic GVHD or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
• Have been diagnosed with or treated other malignant tumors other than AML within 5 years before screening, except for the following conditions: participants with adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer; or received radical treatment Local prostate cancer, ductal carcinoma in situ.
• There are serious systemic diseases: New York Heart Association (NYHA) stage III or IV congestive heart failure; cerebrovascular accident or myocardial infarction or hemodynamic instability caused by arrhythmia within 6 months before signing the informed consent; impaired cardiac function (LVEF\<50%) assessed by echocardiographic scan.
• Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
• Pregnant or lactating women.
• Subjects with radiologically-detected CNS chloromas or CNS 3 disease (presence of ≥ 5/μL white blood cells (WBCs) in cerebral spinal fluid (CSF) and cytospin positive for blasts \[in the absence of a traumatic lumbar puncture\] and/or clinical signs of CNS leukemia such as a cranial nerve palsy from active disease). Subjects with adequately treated CNS leukemia are eligible.
• Human immunodeficiency virus (HIV) seropositivity; hepatitis B surface antigen is positive or HBV DNA is higher than the detection limit of the analysis method; hepatitis C antibody is positive or HCV RNA is higher than the detection limit of the analysis method; syphilis antibody and syphilis rapid plasma reagin are positive; CMV DNA is positive.
• Patients who suffer from allergies for any cytokines or antibodies.
• Contraindications for fludarabine or cyclophosphamide treatment.
• Receiving corticosteroids at \>20 mg daily prednisone dose or equivalent.
• Drug abuse and addiction.
• History of mental disorders.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Department of Hematology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• xi zhang, PhD/MD

  Department of Hematology, Xinqiao Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

xi zhang, PhD/MD

CONTACT

13808310064; zhangxxi@sina.com

ruihao huang, MD

CONTACT

18984398751; 1169731117@qq.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chef of Hematology Department

Study Record Dates

• First Submitted: August 14, 2021
• First Posted: August 23, 2021
• Study Start: September 1, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2023
• Last Updated: August 23, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)