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

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04662294

Collaborator

Yake Biotechnology Ltd. (Industry)

108

Enrollment

Location

Arms

61.9

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Non-hodgkin's Lymphoma Multiple Myeloma	Biological: CD70 CAR T-cells	Early Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Clinical Trial for the Safety and Efficacy of CD 70 CAR T for Patients With CD70 Positive Malignant Hematologic Diseases

Anticipated Study Start Date :

Nov 18, 2021

Anticipated Primary Completion Date :

Jan 15, 2024

Anticipated Study Completion Date :

Jan 15, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: T-ALL	Biological: CD70 CAR T-cells Each subject receive CD70 CAR T-cells by intravenous infusion Other Names: CD70 CAR-T cells injection
Experimental: T-NHL	Biological: CD70 CAR T-cells Each subject receive CD70 CAR T-cells by intravenous infusion Other Names: CD70 CAR-T cells injection
Experimental: AML	Biological: CD70 CAR T-cells Each subject receive CD70 CAR T-cells by intravenous infusion Other Names: CD70 CAR-T cells injection

Arm

Intervention/Treatment

Experimental: T-ALL

Biological: CD70 CAR T-cells

Each subject receive CD70 CAR T-cells by intravenous infusion

Other Names:

CD70 CAR-T cells injection

Experimental: T-NHL

Biological: CD70 CAR T-cells

Each subject receive CD70 CAR T-cells by intravenous infusion

Other Names:

CD70 CAR-T cells injection

Experimental: AML

Biological: CD70 CAR T-cells

Each subject receive CD70 CAR T-cells by intravenous infusion

Other Names:

CD70 CAR-T cells injection

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity (DLT) [Baseline up to 28 days after CD70 targeted CAR T-cells infusion]
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years after CD70 targeted CAR T-cells infusion]
Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

Acute Myeloid Leukemia (AML), Overall response rate (ORR) [At Month 1, 3, 6, 12, 18 and 24]
Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24
AML, Overall survival (OS) [Up to 2 years after CD70 CAR-T cells infusion]
From the first infusion of CD70 CAR-T cells to death or the last visit
AML, Event-free survival (EFS) [Up to 2 years after CD70 CAR-T cells infusion]
From the first infusion of CD70 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit
Non-Hodgkin's lymphoma (NHL), Overall response rate (ORR) [At Month 1, 3, 6, 12, 18 and 24]
Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24
NHL, Overall survival (OS) [Up to 2 years after CD70 CAR-T cells infusion]
From the first infusion of CD70 CAR-T cells to death or the last visit
NHL, Event-free survival (EFS) [Up to 2 years after CD70 CAR-T cells infusion]
From the first infusion of CD70 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse,
Multiple myeloma (MM), Overall response rate (ORR) [At Month 1, 3, 6, 12, 18 and 24]
Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24
MM, Overall survival (OS) [Up to 2 years after CD70 CAR-T cells infusion]
From the first infusion of CD70 CAR-T cells to death or the last visit
MM, Event-free survival (EFS) [Up to 2 years after CD70 CAR-T cells infusion]
From the first infusion of CD70 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse
Quality of life [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12
Activities of Daily Living (ADL) score [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12
Instrumental Activities of Daily Living (IADL) score [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12
Hospital Anxiety and Depression Scale (HADS) score [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inclusion criteria only for AML:

Histologically confirmed diagnosis of CD70 AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);
Relapsed or refractory CD70+ AML (meeting one of the following conditions):
CR not achieved after standardized chemotherapy;
CR achieved following the first induction, but CR duration is less than 12 months;
Ineffectively after first or multiple remedial treatments;
2 or more relapses;
The number of primordial cells in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);
Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
Estimated survival time ≥ 3 months;
ECOG performance status 0 to 2;
Patients or their legal guardians volunteer to participate in the studyand sign the informed consent.

Inclusion criteria only for NHL:

No gender and age limit;
Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
Relapsed or refractory CD70+ NHL (meeting one of the following conditions):
No response or relapse after second-line or above chemotherapy regimens;
Primary drug resistance;
Relapse after auto-HSCT;
At least one assessable tumor lesion per Lugano 2014 criteria

Inclusion criteria only for MM:

Histologically confirmed diagnosis of CD70 multiple myeloma (MM)：
According to the diagnostic criteria of IMWG multiple myeloma, the diagnosis was recurrent / refractory multiple myeloma
Cases with recurrent positive minimal residual disease;
Extramedullary leision which is hard to be eradicated by chemotherapy or radiotherapy.
No gender and age limit;
Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
Estimated survival time ≥ 3 months;
ECOG performance status 0 to 2;
Patients or their legal guardians volunteer to participate in the studyand sign the informed consent.

Common inclusion criteria :

Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
Estimated survival time ≥ 3 months;
ECOG performance status 0 to 2;
Patients or their legal guardians volunteer to participate in the study and sign the informed consent -

Exclusion Criteria:

History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
Pregnant (or lactating) women;
Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
Active infection of hepatitis B virus or hepatitis C virus;
Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;
Previously treated with any CAR-T cell product or other geneticallymodified T cell therapies;
Creatinine >2.5mg/dl, or ALT / AST>3 times of normal amounts, or bilirubin>2.0 mg/dl;
Other uncontrolled diseases that were not suitable for this trial;
Patients with HIV infection;
Any situations that the investigator believes may increase the risk of patients or interfere with the results of study. -