CD 70 CAR T for Patients With CD70 Positive Malignant Hematologic Diseases

NCT ID: NCT04662294

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-18
• Study Completion Date: 2027-01-15

Brief Summary

A Study of CD 70 CAR T for patients with CD70 positive malignant hematologic diseases

Detailed Description

This is a single arm, open-label, single-center study. This study is indicated for CD 70 CAR T for patients with CD70 positive malignant hematologic diseases. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 108 patients will be enrolled. Primary objective is to explore the safety,main consideration is dose-related safety.

Conditions

Acute Myeloid Leukemia; Non-hodgkin's Lymphoma; Multiple Myeloma

Keywords

CAR T-cell therapy; CD70; Acute Myeloid Leukemia; Non-Hodgkin's lymphoma; Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

T-ALL

Group Type: EXPERIMENTAL

CD70 CAR T-cells

Intervention Type: BIOLOGICAL

Each subject receive CD70 CAR T-cells by intravenous infusion

T-NHL

Group Type: EXPERIMENTAL

CD70 CAR T-cells

Intervention Type: BIOLOGICAL

Each subject receive CD70 CAR T-cells by intravenous infusion

AML

Group Type: EXPERIMENTAL

CD70 CAR T-cells

Intervention Type: BIOLOGICAL

Each subject receive CD70 CAR T-cells by intravenous infusion

Interventions

CD70 CAR T-cells

Each subject receive CD70 CAR T-cells by intravenous infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

CD70 CAR-T cells injection

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed diagnosis of CD70 AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);

2. Relapsed or refractory CD70+ AML (meeting one of the following conditions):

1. CR not achieved after standardized chemotherapy;

2. CR achieved following the first induction, but CR duration is less than 12 months;

3. Ineffectively after first or multiple remedial treatments;

4. 2 or more relapses;

3. The number of primordial cells in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);

4. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;

5. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;

6. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;

7. Estimated survival time ≥ 3 months;

8. ECOG performance status 0 to 2;

9. Patients or their legal guardians volunteer to participate in the studyand sign the informed consent.

1. No gender and age limit;

2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);

3. Relapsed or refractory CD70+ NHL (meeting one of the following conditions):

1. No response or relapse after second-line or above chemotherapy regimens;

2. Primary drug resistance;

3. Relapse after auto-HSCT;

4. At least one assessable tumor lesion per Lugano 2014 criteria

1. Histologically confirmed diagnosis of CD70 multiple myeloma (MM)：

1. According to the diagnostic criteria of IMWG multiple myeloma, the diagnosis was recurrent / refractory multiple myeloma

2. Cases with recurrent positive minimal residual disease;

3. Extramedullary leision which is hard to be eradicated by chemotherapy or radiotherapy.

2. No gender and age limit;

3. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;

4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;

5. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;

6. Estimated survival time ≥ 3 months;

7. ECOG performance status 0 to 2;

8. Patients or their legal guardians volunteer to participate in the studyand sign the informed consent.

1. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;

2. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;

3. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;

4. Estimated survival time ≥ 3 months;

5. ECOG performance status 0 to 2;

6. Patients or their legal guardians volunteer to participate in the study and sign the informed consent -

Exclusion Criteria

1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;

2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;

3. Pregnant (or lactating) women;

4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);

5. Active infection of hepatitis B virus or hepatitis C virus;

6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;

7. Previously treated with any CAR-T cell product or other geneticallymodified T cell therapies;

8. Creatinine >2.5mg/dl, or ALT / AST>3 times of normal amounts, or bilirubin>2.0 mg/dl;

9. Other uncontrolled diseases that were not suitable for this trial;

10. Patients with HIV infection;

11. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study. -

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yake Biotechnology Ltd.

INDUSTRY

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

He Huang

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The first affiliated hospital of medical college of zhejiang university

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

He Huang, PhD

Role: CONTACT

Phone: 86-13605714822

Email: hehuangyu@126.com

Yongxian Hu, PhD

Role: CONTACT

Phone: 86-15957162012

Email: huyongxian2000@aliyun.com

Facility Contacts

He Huang, MD

Role: primary

References

Dewulf J, Flieswasser T, Delahaye T, Vangestel C, Miranda A, de Haard H, Jacobs J, Smits E, Van den Wyngaert T, Elvas F. Site-specific 68Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models. EJNMMI Radiopharm Chem. 2023 Apr 24;8(1):8. doi: 10.1186/s41181-023-00194-3.

Reference Type: DERIVED

PMID: 37093350 (View on PubMed)

Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.

Reference Type: DERIVED

PMID: 35468680 (View on PubMed)

Other Identifiers

CD70-001

Identifier Type: -

Identifier Source: org_study_id