A Study of CTA101 UCAR-T Cell Injection in Patients With Relapsed or Refractory CD19+ B-line Hematological Malignancy

A study of CTA101 UCAR-T cell injection in patients with relapsed or refractory CD19+ B-line hematological malignancy

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia; Non-hodgkin Lymphoma
• Intervention / Treatment: Drug: CTA101

Detailed Description

This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-line hematological malignancy: B-ALL and B-NHL. the selection of dose levels and the number of subjects are based on clinical tiral of similar foreign products. 2 groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Hospital of Zhejiang Medical Colleage Zhejiang University
      • Contact: He Huang, MD; Phone Number: 86-13605714822; Email: hehuangyuzj@163.com
      • Contact: Jimin Shi, MD; Phone Number: 86-13857119907; Email: jiminshi@126.com
      • Principal Investigator: He Huang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Inclusion criteria applicable to ALL only:

1. Male or female aged ≥ 3 and <70 years old;
2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);

3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

   1. CR not achieved after standardized chemotherapy;
   2. CR achieved following the first induction, but CR duration is ≤ 12 months;
   3. Ineffective after first or multiple remedial treatments;
   4. 2 or more recurrences;
4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (morphology) and/or >1% (Flow cytometry);
5. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;

Inclusion criteria applicable to NHL only:

1. Male or female aged ≥ 18 and <70 years old;
2. Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2016, including DLBCL(NOS), follicular lymphoma, Chronic lymphoblastic leukemia/small lymphoblastic lymphoma transforms DLBCL, PMBCL and high grade B cell lymphoma;

3. Relapsed or refractory DLBCL (meeting one of the following conditions):

   1. No remission or recurrence after receiving second-line or above second-line chemotherapy;
   2. Primary drug resistance;
   3. Recurrence after autologous hematopoietic stem cell transplantation
4. According to Lugano 2014, there should be at least one evaluable tumor lesion.

Applicable standards for ALL and NHL:

1. HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-);
2. total bilirubin ≤ 51umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L;
3. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
4. No active infection in the lungs, blood oxygen saturation by sucking air is ≥ 92%;
5. Estimated survival time ≥ 3 months;
6. ECOG performance status 0 to 2;
7. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

1. patients with extramedullary lesions, except those with CNSL (CNS-1) under effective control (for ALL patients only);
2. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);
3. Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (for ALL patients only);
4. patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;
5. extensive involvement of gastrointestinal lymphoma (for NHL patients only);
6. radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;
7. Have a history of allergy to any of the components in the cell products;
8. Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
9. According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency;
10. Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
11. Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
12. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
13. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
14. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis).
15. Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;

16. History of other primary cancer, except for the following conditions:

    1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
    2. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;
17. Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
18. Patients with graft-versus-host disease (GVHD);
19. Prior immunizations with live vaccine 4 weeks prior to screening;
20. History of alcoholism, drug abuse or mental illness;
21. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B > 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis infection;
22. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
23. Patients who have participated in any other clinical studies within 2 weeks prior to screening;
24. pregnant and breast-feeding women and the subjects who are fertile and unable to take effective contraceptive measures (regardless of the gender);
25. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

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: Administration of CTA101; Dose escalation follows the standard 3+3 dose escalation design. A total of 2 dose levels are set for subjects.	Drug: CTA101; CTA101 UCAR-T cell injection by intravenous infusion; Other Names: CTA101 UCAR-T cell injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after CTA101 infusion
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after CTA101 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B-ALL, Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24
B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)	Assessment of ORR (ORR = CR + PR ) per Lugano 2014 criteria	weeks 4, 12, months 6, 12, 18 and 24
B-cell acute lymphocytic leukemia (B-ALL), MRD negative overall response rate (MRD- ORR)	Assessment of MRD negative overall response rate (MRD- ORR) at 3 months after CTA101 infusion	3 months
B-ALL, Event-free survival (EFS)	From the first infusion of CTA101 to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit	Month 6, 12, 18 and 24
B-ALL, Overall survival (OS)	From the first infusion of CTA101 to death or the last visit	Month 6, 12, 18 and 24
B-NHL,disease control rate (DCR)	Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria	weeks 12, months 6, 12, 18 and 24

Collaborators and Investigators

• Sponsor: He Huang
• Collaborators: Nanjing Bioheng Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2020
• Primary Completion (Anticipated): January 8, 2022
• Study Completion (Anticipated): May 31, 2027

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): December 28, 2020
• Last Update Submitted That Met QC Criteria: December 24, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: BHCT-CTA101-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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