Anti-CLL1 CAR T-cell Therapy in CLL1 Positive Relapsed/Refractory Acute Myeloid Leukemia (AML)

Pilot Study of the Safety and Efficacy of Anti-CLL1 Chimeric Antigen Receptor Engineered T-Cells in the Treatment of CLL1 Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)

This is a single center, open-label phase 1/2 study to evaluate the safety and efficacy of anti-CLL1 chimeric antigen receptor engineered T cell immunotherapy (CART) in the treatment of CLL1 positive relapsed or refractory acute myeloid leukemia.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: anti-CLL1 CART

Detailed Description

The patients will receive infusion of anti-CLL1 CAR T-cells to confirm the safety and efficacy of anti-CLL1 CAR T-cells in relapsed or refractory acute myeloid leukemia.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lei Yu, Ph.D; Phone Number: (0086)13818629089; Email: ylyh188@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Xiaowen Tang, Ph.D; Phone Number: (0086) 51267781856; Email: xwtang1020@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CLL1 positive relapsed/refractory acute myeloid leukemia
• Age 6-65 years
• Left ventricular ejection fractions ≥ 0.5 by echocardiography
• Creatinine < 1.6 mg/dL
• Aspartate aminotransferase/aspartate aminotransferase < 3x upper limit of normal
• Total bilirubin <2.0 mg/dL
• Karnofsky performance status ≥ 60
• Expected survival time ≥ 3 months (according to investigator's judgement)

Exclusion Criteria:

• Patients are pregnant or lactating
• Uncontrolled active infection
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Active hepatitis B or hepatitis C infection
• Patients with HIV infection
• Patients with history of seizure
• Active central nervous system leukemia

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 positive relapsed or refractory acute myeloid leukemia	Biological: anti-CLL1 CART; Split intravenous infusion of anti-CLL1 CAR T cells [dose escalating infusion of (5-20)x10^6 anti-CLL1 CAR T cells/kg].

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	Adverse events are evaluated with CTCAE V5.0	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR includes CR, CRi, MLFS and PR. Complete remission (CR)#Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0x 10^9/L; platelet count >100x10^9/L. CR with incomplete hematologic recovery (CRi)#All CR criteria except for residual neutropenia (<1.0x10^9/L) or thrombocytopenia (<100x10^9/L). Morphologic leukemia-free state (MLFS): Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. Partial remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.	2 years
overall survival (OS)	The date of enrollment to the date of death from any cause	2 years
Event-free survival (EFS)	Time from enrollment to the date of primary refractory disease, or relapse from CR or CRi, or death from any cause	2 years
Cumulative incidence of relapse(CIR)	Time from the date of achievement of a remission to the date of relapse	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: AML; CLL1; CART
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: UnicarTherapy2021001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No