CD19 CAR-T consolidation for adolescents and adults with B-ALL who cannot have a transplant

Clinical Study on the Efficacy and Safety of CD19 CAR-T Cell Infusion as Consolidation Therapy in Adolescent and Adult Patients With Acute B-Lymphoblastic Leukemia Who Are Ineligible for Allogeneic Hematopoietic Stem Cell Transplantation

This treatment tries CD19 CAR-T cell infusions to see if they help adolescents and adults with B-ALL who are unable to get an allogeneic stem cell transplant stay in remission.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 14 Years to 80 Years
• Sex: All
• Sponsor: Zhujiang Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy, chimeric antigen receptor
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT07072494 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm prospective phase 1/2 study will enroll about 30 adolescent and adult patients with CD19-positive B-ALL who are ineligible for allogeneic hematopoietic stem cell transplantation. Participants who are in complete remission after chemotherapy or immunotherapy will receive lymphodepleting chemotherapy followed by a single infusion of CD19-directed CAR-T cells and will be followed for short- and long-term outcomes over roughly three years. The study will record rates of complete remission and MRD-negativity, survival outcomes, and monitor safety with particular attention to cytokine release syndrome and neurotoxicity. Early intervention and established supportive care measures for key toxicities will be implemented per standard guidelines.

Who should consider this trial

Good fit: Ideal candidates are CD19-positive adolescents and adults (ages 14–80) with B-ALL who have achieved remission after prior therapy but are ineligible for, lack a donor for, or decline allo-HSCT and have ECOG performance status 0–2.

Not a fit: Patients with CD19-negative disease, uncontrolled comorbidities or infections, very poor performance status, or those who are eligible for and choose standard allo-HSCT are unlikely to benefit from this investigational consolidation approach.

Why it matters

Potential benefit: If successful, this approach could offer a transplant-alternative consolidation that increases remission durability and survival for patients with B-ALL who cannot receive an allogeneic transplant.

How similar studies have performed: CD19-directed CAR-T therapies have produced high remission rates in relapsed/refractory B-ALL, but using CAR-T specifically as consolidation in transplant-ineligible patients is less well established.

Eligibility criteria

Inclusion Criteria:

1. The subject has voluntarily agreed to participate, signed the informed consent form, and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
2. The subject has been clinically diagnosed with newly diagnosed or refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL), including Burkitt lymphoma leukemia and blast-phase chronic myeloid leukemia, and has achieved complete remission (defined as \<5% bone marrow blasts, no peripheral blood blasts, and no extramedullary leukemia) after chemotherapy or immunotherapy, but is either ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT), lacks a suitable donor, or declines transplantation.
3. Aged between 14 and 80 years (inclusive), male or female.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
5. At the time of screening, leukemia cells in the bone marrow or peripheral blood must be confirmed as CD19-positive by flow cytometry at initial or relapse diagnosis.
6. An expected survival of more than three months from the date of signing the informed consent form.
7. Satisfactory liver, kidney, cardiac, and pulmonary function, defined as:

   1. Creatinine ≤2× upper limit of normal (ULN);
   2. Left ventricular ejection fraction (LVEF) ≥50%;
   3. Blood oxygen saturation \>92%;
   4. Total bilirubin ≤2× ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× ULN.
8. Adequate venous access for cell collection and meeting the following hematologic criteria:

   Hemoglobin ≥80 g/L Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L Platelet count ≥75 × 10⁹/L If the above criteria are not met, the investigator may determine eligibility for mononuclear cell collection.
9. Female subjects of childbearing potential must have a negative serum pregnancy test (women who have undergone surgical sterilization or have been postmenopausal for at least two years are considered non-fertile). Male and female subjects of reproductive potential must agree to use contraception during the study.

Exclusion Criteria:

1. Presence of mixed-lineage leukemia or biphenotypic leukemia.
2. Prior treatment with CAR-T cell therapy before screening or conditioning.
3. Patients with bone marrow failure syndromes associated with genetic disorders, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndromes.
4. Any of the following viral infections:

   Hepatitis B virus (HBV) DNA detectable above the lower limit of quantification. Positive hepatitis C virus antibody (HCV-Ab). Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA detectable above the lower limit of quantification.

   Positive human immunodeficiency virus (HIV) antibody test.
5. History of or current malignancy within the past five years (excluding patients with a low risk of recurrence after curative treatment and more than five years of follow-up, as determined by the investigator).
6. Any of the following cardiac conditions:

   New York Heart Association (NYHA) Class III or IV congestive heart failure. Severe arrhythmia requiring treatment or clinically significant conduction abnormalities on ECG, including QTc interval ≥480 ms (QTcB = QT/√RR).

   Uncontrolled hypertension despite standard treatment (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg) or pulmonary hypertension.

   Unstable angina. Myocardial infarction, coronary artery bypass grafting, or stent placement within six months before cell infusion.

   Clinically significant valvular heart disease. Other cardiac diseases deemed inappropriate for study participation by the investigator.
7. Uncontrolled epilepsy, a history of cerebrovascular ischemia/hemorrhage, cerebellar disease, or other active central nervous system (CNS) disorders.
8. Clinically significant pericardial or pleural effusion at screening.
9. History of deep vein thrombosis or pulmonary embolism within six months before screening.
10. Known hypersensitivity to any component of the study treatment.
11. Live vaccine administration within six weeks before screening.
12. Severe, uncontrolled, active infection at screening.
13. Participation in other interventional clinical trials and receipt of an investigational agent, including:

    An unapproved investigational drug within three months before cell infusion. A marketed drug within fewer than five half-lives before cell infusion.
14. Any other conditions deemed unsuitable for study participation by the investigator.
15. Physical or cognitive conditions that impair the ability to provide informed consent or comply with study procedures, or unwillingness or inability to adhere to study requirements.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Zhujiang Hospital — Guangzhou, Guangdong, China (Recruiting)
• Zhujiang Hospital — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Sanfang Tu, Doctor

Conditions Acute Lymphoblastic Leukemia; Chimeric Antigen Receptor T-Cell Immunotherapy; CD19