Using CAR T cells to treat certain types of blood cancers

Application of the Autologous CAR T Cells (Tarcidomgen Kimleucel) in the Treatment of Refractory and Relapsed CD19+ B Cell Neoplasms

This study is testing a new CAR T cell therapy to see if it can help adults with tough-to-treat blood cancers like certain types of leukemia and lymphoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: FamiCordTx (Industry-sponsored)
• Drugs / interventions: CART, chemotherapy, cyclophosphamide, fludarabine, CAR T
• Locations: 2 sites (Warsaw, Ul. Banacha 1a and 1 other locations)
• Trial ID: NCT06593145 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and preliminary efficacy of FCTX-CL19-1 (Tarcidomgen Kimleucel), an investigational product containing autologous anti-CD19 CAR T cells, in patients with refractory and relapsed CD19+ B cell neoplasms. The study is an open-label, one-arm phase I trial focusing on adult patients aged 18-65 who have specific types of B-cell cancers, including acute lymphoblastic leukemia, mantle cell lymphoma, and large B-cell lymphoma. Participants will receive intravenous administration of the CAR T cell therapy, and the trial aims to assess both safety and potential for remission in these challenging cases.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with refractory or relapsed CD19+ B cell neoplasms who have undergone at least two lines of systemic treatment.

Not a fit: Patients with non-CD19 expressing tumors or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with resistant B-cell cancers, potentially leading to remission.

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:

1. Adult patients 18-65 both inclusive;
2. Diagnosis of:

   1. Refractory B-ALL (acute lymphocytic leukemia) - relapse after hematopoietic cell transplantation, second or more relapse in patients when transplantation is contraindicated)
   2. Large B-cell lymphoma including DLBCL NOS, lymphoma with high level of malignancy, follicular lymphoma transformed to DLBCL and primary mediastinal lymphoma - refractory or relapse or after at least 2 lines of systemic treatment)
   3. Mantle cell lymphoma (MCL) - relapsing or refractory after at least 2 lines of systemic treatment; Diagnostics of individual diagnoses (criteria for complete remission and partial responses for individual disease entities) was developed on the basis of current (July 2022) recommendations of experts of the Polish Society of Clinical Oncology
3. Confirmed CD19 expression on malignant cells;
4. General condition measured by ECOG (Eastern Cooperative Oncology Group) ≤ 1;
5. Patient's weight between 40 kg - 130 kg
6. Sufficient general condition of organs on screening visit:

   1. ALT/AST \<2,5 of UNL and bilirubin \<1,5 mg/dl (\<4 mg/dl for patients with Gilbert syndrome)
   2. Ejection fraction (EF) \>50% confirmed in ECHO with no signs of exudation in pericardium during 6 weeks before screening
   3. Saturation of arterial blood \>93% with no oxygen insufflation, with no significant exudation in pleural cavity
   4. Serum creatinine clearance \>60 ml/min (by Cockcroft-Gault formula);
7. Negative result for HCV, HBV, HIV, Syphilis;
8. Negative test for pregnancy (serum or urine) in the screening visit and/or 7 days before leucapheresis and 7 days before lymphodepleting therapy in women in reproductive age;
9. Assumption of at least 12 months of survival time from screening visit;
10. Agreement to maintain sufficient method of contraception from the date of signing informed consent to 6 months after CART therapy;
11. The last dose of SARS-CoV-2 vaccination taken at least 6 months prior to study enrollment
12. Capable of providing written informed consent;
13. Patients polish native language speaking or fluent in polish language

Exclusion Criteria:

1. Any significant CNS diseases that preceded and not connected with relapse (including seizures, paresis, aphasia, stroke or CNS bleeding, severe brain trauma, dementia, Parkinson's disease, any disease affecting cerebellum, psychosis and diseases involving lack of coordination or movement);
2. Bulky or rapidly progressing disease;
3. Less than 3 months after allo-HSCT transplantation or DLI before screening;
4. The need for high-dose chemotherapy less than 4 weeks before the scheduled apheresis;
5. Concomitant presence of another malignancy and another malignancy diagnosed up to 2 years before inclusion to this trial;
6. Patient's weight below 40 kg and above 130kg
7. Any active bacterial, viral or fungal infection including SARS-CoV2;
8. Latent HBV/HCV/HIV/Syphilis infection;
9. Any other concomitant disease which in the opinion of the investigator would be interfering with the safety of participant in the trial
10. Allergic to penicillin, streptomycin and amphotericin B;
11. Intolerance to cyclophosphamide or fludarabine during previous treatment with these drugs;
12. Chronic systemic immunosuppression treatment (i.e. cyclosporin). Corticosteroids are allowed up to dexamethasone dose of 4 mg a day or equal of this dose;
13. Systemic immunosuppression treatment of acute and/or chronic Graft-versus host disease (GvHD) connected to earlier allogeneic HSCT treatment;
14. Pregnancy;
15. Women in reproductive age as well as men (regardless of age) that do not agree to maintain effective method of contraception during the trial, lactated women can be included into the trial unless declaration of stopping breast feeding during the whole trial time;
16. Unable to provide informed consent for this trial;
17. Lack of actual vaccination against SARS-CoV2 by vaccine accepted to use in the EU;
18. Patients who are not fluent in polish language;
19. Previous use of anti-CD19 CART therapy

Where this trial is running

Warsaw, Ul. Banacha 1a and 1 other locations

• Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego - Centralny Szpital Kliniczny — Warsaw, Ul. Banacha 1a, Poland (Recruiting)
• Uniwersyteckie Centrum Kliniczne Gdańskiego Uniwersytetu Medycznego - Katedra i Klinika Hematologii i Transplantologii — Gdansk, Ul. Smoluchowskiego 17, Poland (Recruiting)

Study contacts

• Study coordinator: Natalia Żmijewska

Conditions Acute Lymphoblastic Leukemia; Mantle Cell Lymphoma; Large B-cell Lymphoma