CAR-T cell therapy for patients with relapsed or refractory blood cancers in the central nervous system

Clinical Trial for the Safety and Efficacy of CAR-T Cells Therapy for Patients With the Central Nervous System Involvement of Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia or B-cell Non-Hodgkin's Lymphoma

This study is testing a new CAR-T cell therapy to see if it can safely help patients with relapsed or hard-to-treat blood cancers in the brain, like acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 3 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang University (other)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT04532203 on ClinicalTrials.gov

What this trial studies

This study investigates the use of CAR-T cell therapy in patients with relapsed or refractory central nervous system hematological malignancies, specifically targeting acute lymphoblastic leukemia and non-Hodgkin's lymphoma. It is a single-arm, open-label trial conducted at a single center, enrolling two groups of patients with a total of 72 participants. The primary objective is to assess the safety of the treatment, with a focus on dose-related safety based on previous clinical trials of similar therapies.

Who should consider this trial

Good fit: Ideal candidates include males and females aged 3-70 with relapsed or refractory CD19+ acute lymphoblastic leukemia or B-cell non-Hodgkin's lymphoma.

Not a fit: Patients with hematological malignancies that are not CD19+ or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat blood cancers.

How similar studies have performed: Other studies using CAR-T cell therapy for similar conditions have shown promising results, indicating a potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Inclusion criteria only for B-ALL:

  1. Male or female aged 3-70 years;
  2. Histologically confirmed diagnosis of B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
  3. Relapsed or refractory CD19+ B-ALL (meeting one of the followingconditions):

     1. CR not achieved after standardized chemotherapy;
     2. CR achieved following the first induction, but CR duration isless than 12 months;
     3. Ineffectively after first or multiple remedial treatments;
     4. 2 or more relapses;
  4. The number of primordial cells (lymphoblast and prolymphocyte)in bone marrow is\>5% (by morphology), and/or \>1% (by flowcytometry);
  5. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
* Inclusion criteria only for B-NHL:

  1. Male or female aged 18-75 years;
  2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHOClassification Criteria for Lymphoma (2016);
  3. Relapsed or refractory B-NHL (meeting one of the followingconditions):

     1. No response or relapse after second-line or abovechemotherapy regimens;
     2. Primary drug resistance;
     3. Relapse after auto-HSCT;
  4. At least one assessable tumor lesion per Lugano 2014 criteria;
* Common inclusion criteria for B-ALL and B-NHL:

  1. Highly suspected or confirmed central nervous system involvement of hematological malignancies;
  2. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
  3. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
  4. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
  5. Estimated survival time ≥ 3 months;
  6. ECOG performance status 0 to 2;
  7. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

Subjects with any of the following exclusion criteria were not eligible for this trial:

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 urinarytractinfectionand 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 genetically-modified T cell therapies;
8. Creatinine\>2.5mg/dl, or ALT / AST \> 3 times of normal amounts,orbilirubin\>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 ofpatients or interfere with the results of study.

Where this trial is running

Hangzhou, Zhejiang

• The First Affiliated Hospital，College of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: He Huang, PhD

Conditions: Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma, CAR T-cell therapy