CD20/CD22 targeted CAR T-cell therapy for blood cancers

A Study of CD20/CD22 Targeted CAR T-cell Therapy for Relapsed or Refractory Lymphoid Malignancies

This study is testing a new CAR T-cell therapy that targets specific proteins on blood cancer cells to see if it can help patients whose cancer hasn't responded to other treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 3 Years to 70 Years
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: CAR T, chemotherapy, CAR-T
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT04283006 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of CD20/CD22 targeted CAR T-cell therapy in patients with relapsed or refractory lymphoid hematological malignancies. The study aims to treat patients who have not responded to standard therapies, utilizing a single-arm, open-label approach at a single center. The therapy targets specific proteins on the surface of cancer cells to enhance the immune response against these malignancies. Previous studies have shown promise with CAR T-cell therapies, and this trial seeks to further validate the dual-target approach.

Who should consider this trial

Good fit: Ideal candidates include males and females aged 3 to 70 with relapsed or refractory CD19+ B-ALL or certain types of non-Hodgkin lymphoma.

Not a fit: Patients with hematological malignancies that do not express CD20 or CD22 may not benefit from this therapy.

Why it matters

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

How similar studies have performed: Other studies have shown success with CAR T-cell therapies targeting CD19, but the dual-target approach of CD20/CD22 is still being explored.

Eligibility criteria

Criteria:

Inclusion Criteria:

Inclusion criteria applicable to ALL only:

1. Male or female aged ≥ 3 and \<70 years old;
2. Histologically confirmed diagnosis of CD19+ 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 following conditions):

   1. CR not achieved after standardized chemotherapy;
   2. CR achieved following the first induction, but CR duration is ≤ 12 months;
   3. Ineffective after first or multiple remedial treatments;
   4. 2 or more recurrences;
4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is \>5% (morphology) and/or \>1% (Flow cytometry);
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 applicable to NHL only:

1. Male or female aged ≥ 18 and \<70 years old;
2. Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2016, including DLBCL(NOS), follicular lymphoma, Chronic lymphoblastic leukemia/small lymphoblastic lymphoma transforms DLBCL, PMBCL and high grade B cell lymphoma;
3. Relapsed or refractory DLBCL (meeting one of the following conditions):

   1. No remission or recurrence after receiving second-line or above second-line chemotherapy;
   2. Primary drug resistance;
   3. Recurrence after autologous hematopoietic stem cell transplantation;
4. According to Lugano 2014, there should be at least one evaluable tumor lesion.

Applicable standards for ALL and NHL:

1. HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-);
2. total bilirubin ≤ 51umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L;
3. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
4. No active infection in the lungs, blood oxygen saturation by sucking air 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:

1. patients with extramedullary lesions, except those with CNSL (CNS-1) under effective control (for ALL patients only);
2. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);
3. Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (for ALL patients only);
4. Patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;
5. Extensive involvement of gastrointestinal lymphoma (for NHL patients only);
6. Radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;
7. Have a history of allergy to any of the components in the cell products;
8. Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
9. According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency;
10. Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
11. Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
12. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
13. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
14. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis).
15. Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;
16. History of other primary cancer, except for the following conditions:

    1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
    2. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;
17. Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
18. Patients with graft-versus-host disease (GVHD);
19. Prior immunizations with live vaccine 4 weeks prior to screening;
20. History of alcoholism, drug abuse or mental illness;
21. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B \> 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis infection;
22. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
23. Patients who have participated in any other clinical studies within 2 weeks prior to screening;
24. Pregnant and breast-feeding women and the subjects who are fertile and unable to take effective contraceptive measures (regardless of the gender);
25. 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 Hospital of Zhejiang Medical Colleage Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: He Huang, MD

Conditions Relapsed and Refractory; Lymphoid Hematological Malignancies; lymphoid hematological malignancies; CAR T-cell therapy; CD20/CD22