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

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Multiple Myeloma; Non-hodgkin's Lymphoma
• Intervention / Treatment: Biological: CD70 CAR T-cells

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 Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

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 CD70 targeted CAR T-cells infusion
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 18, 2021
• Primary Completion (Anticipated): January 15, 2024
• Study Completion (Anticipated): January 15, 2027

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: December 5, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 4, 2021
• Last Update Submitted That Met QC Criteria: October 26, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Multiple Myeloma; Non-Hodgkin's lymphoma; CAR T-cell therapy; CD70
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia; Lymphoma; Multiple Myeloma; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Hematologic Diseases
• Other Study ID Numbers: CD70-001

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