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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04662294
• Other study ID #: CD70-001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 18, 2021
• Est. completion date: January 15, 2027

Study information

• Verified date: December 2020
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: January 15, 2027
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Inclusion criteria only for AML:

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.

Inclusion criteria only for NHL:

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

Inclusion criteria only for MM:

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.

Common inclusion criteria :

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. -

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Hematologic Diseases
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Non-hodgkin's Lymphoma

Intervention

Biological:
• CD70 CAR T-cells
Each subject receive CD70 CAR T-cells by intravenous infusion

Locations

Country	Name	City	State
China	The first affiliated hospital of medical college of zhejiang university	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Yake Biotechnology Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after CD70 targeted CAR T-cells infusion
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after CD70 targeted CAR T-cells infusion
Secondary	Acute Myeloid Leukemia (AML), Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
Secondary	AML, Overall survival (OS)	From the first infusion of CD70 CAR-T cells to death or the last visit	Up to 2 years after CD70 CAR-T cells infusion
Secondary	AML, Event-free survival (EFS)	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	Up to 2 years after CD70 CAR-T cells infusion
Secondary	Non-Hodgkin's lymphoma (NHL), Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
Secondary	NHL, Overall survival (OS)	From the first infusion of CD70 CAR-T cells to death or the last visit	Up to 2 years after CD70 CAR-T cells infusion
Secondary	NHL, Event-free survival (EFS)	From the first infusion of CD70 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse,	Up to 2 years after CD70 CAR-T cells infusion
Secondary	Multiple myeloma (MM), Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
Secondary	MM, Overall survival (OS)	From the first infusion of CD70 CAR-T cells to death or the last visit	Up to 2 years after CD70 CAR-T cells infusion
Secondary	MM, Event-free survival (EFS)	From the first infusion of CD70 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse	Up to 2 years after CD70 CAR-T cells infusion
Secondary	Quality of life	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	Activities of Daily Living (ADL) score	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	Instrumental Activities of Daily Living (IADL) score	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	Hospital Anxiety and Depression Scale (HADS) score	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	At Baseline, Month 1, 3, 6, 9 and 12