Using engineered immune cells to treat relapsed or refractory B-cell cancers
Allogeneic Natural Killer T-Cells Expressing CD19 Specific Chimeric Antigen Receptor and Interleukin-15 in Relapsed or Refractory B-Cell Malignancies
This study is testing whether specially engineered immune cells can help people with tough-to-treat B-cell cancers, like certain lymphomas and leukemias, by better targeting and destroying cancer cells.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 48 (estimated) |
| Ages | 3 Years to 75 Years |
| Sex | All |
| Sponsor | Baylor College of Medicine Academic / other |
| Drugs / interventions | ibrutinib, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 2 sites (Houston, Texas and 1 other locations) |
| Trial ID | NCT03774654 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the use of CD19.CAR allogeneic NKT cells to treat patients with relapsed or refractory B-cell malignancies, including various forms of lymphoma and leukemia. The approach involves gene transfer to enhance immune cells, allowing them to target and destroy cancer cells more effectively. Patients will receive a dose of these engineered cells after undergoing a preparatory regimen with cyclophosphamide and fludarabine to reduce their own immune cells. The study will monitor patients for long-term effects over a period of 15 years.
Who should consider this trial
Good fit: Ideal candidates include adults with CD19-positive B-cell lymphoma or leukemia who have relapsed or are refractory after multiple lines of therapy.
Not a fit: Patients with B-cell malignancies that are not CD19-positive or those who have not undergone prior therapies may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell malignancies.
How similar studies have performed: Other studies using CAR T-cell therapies have shown promising results, indicating potential success for this novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Treatment Inclusion Criteria:
1. Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL).
2. The disease is:
Cohort A (non-ALL patients):
1. Relapsed or refractory after two or more lines of therapy, including a CD20 antibody, if an indolent lymphoma.
2. Relapsed or refractory after two or more lines of therapy, including ibrutinib and venetoclax, if CLL.
3. Relapsed or refractory after two or more lines of therapy, including a CD20 antibody and an anthracycline, and the patient is ineligible for autologous stem cell transplantation, if an aggressive or highly aggressive lymphoma.
* Ineligibility for autologous stem cell transplantation includes non-responsive disease after salvage therapy and failure to mobilize stem cells for transplant.
Cohort B (ALL patients)
a. Relapsed or refractory after two or more lines of therapy, if ALL.
3. Measurable disease by current criteria (Lugano criteria for lymphomas, IWG criteria for CLL, and detectable disease for ALL).
4. Age ≥ 3 and ≤75 years.
5. Bilirubin \< 2 times (3 times if Gilbert syndrome) upper limit of normal
6. AST and ALT less than 5 times the upper limit of normal.
7. Estimated GFR ≥ 50 mL/min.
8. Pulse oximetry of ≥ 90% on room air
9. Karnofsky or Lansky score of ≥ 70.
10. Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
11. Life expectancy of greater than 12 weeks.
12. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
13. Patients must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
Treatment Exclusion Criteria:
1. Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks.
2. History of hypersensitivity reactions to murine protein-containing products.
3. History of grade 2 to 4 graft-versus-host disease (GVHD)
4. Pregnant or lactating.
5. Active infection with HIV or HTLV.
6. Active infection with HBV or HCV.
7. Uncontrolled active bacterial, fungal or other viral infection.
Where this trial is running
Houston, Texas and 1 other locations
- Houston Methodist Hospital — Houston, Texas, United States (Recruiting)
- Texas Children's Hospital — Houston, Texas, United States (Not_yet_recruiting)
Study contacts
- Principal investigator: Carlos Ramos, MD — Baylor College of Medicine
- Study coordinator: Carlos Ramos, MD
- Email: caramos@bcm.edu
- Phone: (832) 824-4817
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.