CD70 CAR T-cell therapy for blood cancers

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

This study is testing a new CAR T-cell therapy for blood cancers to see if it is safe and effective for patients with certain types of leukemia and lymphoma.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, CAR T
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT04662294 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of CD70 CAR T-cell therapy in patients with CD70 positive malignant hematologic diseases, including acute myeloid leukemia, non-Hodgkin's lymphoma, and multiple myeloma. It is a single-arm, open-label, single-center trial that aims to enroll 108 patients. The primary objective is to explore dose-related safety based on previous clinical trials of similar therapies.

Who should consider this trial

Good fit: Ideal candidates include patients with relapsed or refractory CD70 positive acute myeloid leukemia who meet specific clinical criteria.

Not a fit: Patients with CD70 negative hematologic diseases or those with active infections may not benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with CD70 positive blood cancers.

How similar studies have performed: Other studies have shown promise with CAR T-cell therapies targeting different antigens, suggesting potential for success with this novel approach.

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. -

Where this trial is running

Hangzhou, Zhejiang

• The first affiliated hospital of medical college of zhejiang university — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: He Huang, PhD

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