Leukemia, Plasma Cell
Conditions
Brief summary
Phase II, pilot, open-label, prospective, multicenter, non-randomized study to evaluate the safety and efficacy of ARI0002h (cesnicabtagene autoleucel) in 20 patients with newly diagnosed primary plasma cell leukemia (PCL). The study population is patients between 18 and 75 years of age with newly diagnosed primary plasma cell leukemia (pPCL), with a life expectancy of more than 3 months. The primary objective is to assess the safety and efficacy of CARTBCMA ARI0002h (cesnicabtagene autoleucel) after initial treatment to induce response in patients with newly diagnosed primary plasma cell leukaemia.
Interventions
GENETICARI0002h
* Treatment with ARI0002h cells * Other names: CARTBCMA\_J22.9-h:CD8TM:4-1BB:CD3. Adult differentiated autologous T cells from peripheral blood, expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-BCMA (TNFRSF17) specificity conjugated to the 4-1BB co-stimulatory domain and the CD3z signalling domain that has been humanized.
Sponsors
Fundacion Clinic per a la Recerca Biomédica
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients between 18 and 75 years old diagnosed with newly diagnosed primary plasma cell leukemia (the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma), according to International Myeloma Working Group (IMWG). 2. Disease measurable at diagnosis by monoclonal component in serum or urine, or by free light chains in serum according to the eligibility criteria for clinical trials of the International Myeloma Working Group. 3. ECOG Performance Status from 0 to 2 4. Life expectancy greater than 3 months. 5. Adequate venous access and absence of contraindications for lymphoapheresis. 6. Patients who, after being informed, give their consent by signing the Informed Consent Document. 7. Up to two cycles of previous treatment for symptomatic control will be allowed before inclusion.
Exclusion criteria
1. No previous treatments, except for induction therapy for primary plasma cell leukemia. 2. Administration of any anti-BCMA therapy as part of induction 3. Not having achieved at least a minimal response with induction treatment (IMWG criteria) 4. Absolute lymphocyte count \<0.1x109/L 5. Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent). 6. Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer, except for non-melanoma skin cancer or completely resected in situ carcinoma. 7. Active infection requiring treatment. 8. Active HIV, HBV, or HCV infection. 9. Uncontrolled medical illness 10. Severe organ impairment that meets any of the following criteria: EF\<40%, DLCO \<40%, GFR \<30 ml/min, bilirubin \>3 times the upper limit of normality (unless due to Gilbert syndrome) 11. Previous diagnosis of symptomatic AL amyloidosis, 12. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at the screening phase. 13. Women of childbearing potential, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective contraceptive methods\* from the beginning of the study to completion of the study. 14. Men who are unable or unwilling to use highly effective contraceptive methods\* from the beginning of the study to completion of the study. 15. Contraindication to receive lymphodepletive chemotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 3 months after the first infusion | Overall response rate (ORR) during the initial 3 months after the first infusion (at least presenting a partial response according to the International Myeloma Working Group criteria). |
| Rate of patients who develop cytokine release syndrome and/or neurological toxicity | 30 days after CARTBCMA administration | Rate of patients who develop cytokine release syndrome and/or neurological toxicity in the first 30 days after CARTBCMA administration, according to the criteria and grading defined in the international consensus document |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | From day 28 after infusion to study completion, an average of 24 months | Duration of response calculated from the time of first disease evaluation |
| Response rates | During the first year after administration | Response rates |
| Complete response rate | at 3, 6, and 12 months after the first infusion | Complete response rate |
| Overall response rate | at 6, and 12 months after the first infusion | Overall response rate |
| Time to complete response | through study completion, an average of 24 months | Time to complete response |
| Time to best response | through study completion, an average of 24 months | Time to best response |
| MRD negative rate in bone marrow | at 3, 6 12 and 24 months | MRD negative rate in bone marrow by flow cytometry |
| Presence of prolonged cytopenias | between 4 weeks after infusion and study completion | Presence of prolonged cytopenias, defined as a grade 4 decrease in peripheral blood neutrophil or platelet counts for more than 4 weeks after infusion. |
| Progression-free survival | through study completion, an average of 24 months | defined as the time between administration of ARI0002h and disease progression or death. Patients who are alive and in complete remission will be censored at the time of the last follow-up. |
| Progression-free survival at 12 months after the first administration | 12 months | Progression-free survival at 12 months after the first administration, defined as the time elapsed between the administration of ARI0002h and disease progression or death. Patients who are alive and in complete remission will be censored at the time of the last follow-up. |
| Overall survival | through study completion, an average of 24 months | Overall survival, defined as the time between infusion of ARI0002h and death of the patient from any cause. Living patients will be censored at the time of last follow-up. |
| Presence of infusion reactions | through study completion, an average of 24 months | Presence of infusion reactions, understood as the appearance of any of the following symptoms after the intravenous administration of CARTBCMA: cardiac events, chills, dyspnea, fatigue, sudden hypertension, hypotension, nausea, pain, fever, rash or urticaria. |
| Tumour lysis syndrome | through study completion, an average of 24 months | Tumour lysis syndrome |
| Cytokine release syndrome | through study completion, an average of 24 months | Cytokine release syndrome. According to the criteria and grading defined in the international consensus document |
| Neurological toxicity | through study completion, an average of 24 months | Neurological toxicity according to the criteria and grading defined in the international consensus document (Lee, Santomasso et al. 2019) |
| Response rate of extramedullary disease | at 3, 6 and 12 months. | Response rate of extramedullary disease by PET-CT |
| Quality of life of patients | during the first year after infusion | Quality of life during the first year after infusion according to the Quality of life questionnaire 2008 EuroQol Group EQ-5D |
Countries
Spain
Contacts
Primary ContactCarlos Fernandez de Larrea, MD, PhD
Backup ContactMaria Joyera
Outcome results
None listed