Clinical trial NCT04662294: CD 70 CAR T for Patients With CD70 Positive Malignant Hematologic Diseases
Official title: Clinical Trial for the Safety and Efficacy of CD 70 CAR T for Patients With CD70 Positive Malignant Hematologic Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
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
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2020-12-10
Enrollment: 108
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. -

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after CD70 targeted CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after CD70 targeted CAR T-cells infusion
Secondary outcomes:
measure: Acute Myeloid Leukemia (AML), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: AML, Overall survival (OS)
timeFrame: Up to 2 years after CD70 CAR-T cells infusion
measure: AML, Event-free survival (EFS)
timeFrame: Up to 2 years after CD70 CAR-T cells infusion
measure: Non-Hodgkin's lymphoma (NHL), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: NHL, Overall survival (OS)
timeFrame: Up to 2 years after CD70 CAR-T cells infusion
measure: NHL, Event-free survival (EFS)
timeFrame: Up to 2 years after CD70 CAR-T cells infusion
measure: Multiple myeloma (MM), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: MM, Overall survival (OS)
timeFrame: Up to 2 years after CD70 CAR-T cells infusion
measure: MM, Event-free survival (EFS)
timeFrame: Up to 2 years after CD70 CAR-T cells infusion
measure: Quality of life
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Activities of Daily Living (ADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Instrumental Activities of Daily Living (IADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Hospital Anxiety and Depression Scale (HADS) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
References:
citation: 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.