Clinical trial NCT05982275: Trial of an Investigational Drug After Rejecting the Relapse of an Allogeneic Transplant
Official title: Anti-BCMA Chimeric Antigen Receptor (CARTemis-1) T-lymphocyte Therapy in the Treatment of Patients With Multiple Myeloma in Relapse After Allogeneic Transplant: Endothelial Growth Factor Receptor Expression as a Control Mechanism of Treatment-derived Complications
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Allogeneic Stem Cell Transplantation
Keywords: Chimeric antigen receptor-T cell therapy
B-Cell Maturation Antigen
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2023-08-08
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Most patients with multiple myeloma (MM) die due to relapse resistant to current treatment, including treatment with anti-B cell maturation antigen (BCMA) CAR-T cells. To overcome some of the potential limitations of this therapy, a new and optimized Anti-BCMA CAR-T has been developed, with the aim of using it in patients with MM who relapse after Allogeneic Haematopoietic Haematopoietic Progenitor. This trial is a prospective phase I/II trial with a 3+3 design. Once Dose Limiting Toxicity is identified, Phase II will begin to assess the efficacy of the procedure.

Detailed description: This trial is a prospective phase I/II trial with a 3+3 design. Once Dose Limiting Toxicity is identified (up to a maximum dose of 6x106 CAR-T/kg divided over 2 days), phase II of the trial will begin to assess the efficacy of the procedure.

A number of 25 patients will be included to evaluate.

Eligibility criteria: Inclusion Criteria:

1. Patients \> 18 years old with a diagnosis of post-allogeneic transplant relapse multiple myeloma.
2. Measurable disease at the time of screening
3. Previous treatment with ≥2 lines before and/or after allogeneic transplant.
4. Patients who are not receiving immunosuppressants at least 1 month before inclusion and who do not have active graft-versus-host disease.
5. Eastern Cooperative Oncology Group functional status from 0 to 1.
6. Life expectancy greater than 3 months (at the time of screening)
7. Patients who give their consent by signing the Informed Consent document.

Exclusion Criteria:

1. Active systemic immunosuppressive treatment
2. Patients who have previously received treatment with CAR-T Anti-BCMA.
3. Absolute lymphocyte count \<0.2x109/L
4. Previous neoplasm, except if it has been in complete remission \>3 years, with the exception of skin carcinoma (non-melanoma)
5. Active infection requiring treatment.
6. Active HIV, hepatitis B virus or hepatitis C virus infection.
7. Uncontrolled medical illness.
8. Severe organic disease that meets any of the following criteria: left ventricular ejection fraction \<40%, carbon monoxide diffusion test \<40%, glomerular filtration rate \<50 ml/min, bilirubin \>3 normal value (except Gilbert syndrome).
9. Previous diagnosis of symptomatic amyloid light chain or primary amyloidosis or POEMS Syndrome.
10. Pregnant or lactating women.
11. Women of childbearing age, unable or unwilling to use highly effective contraceptive methods.
12. Men who cannot or do not wish to use highly effective contraceptive methods. The partner of the male participants, if they are women of childbearing age, must also use highly effective contraceptive methods during the study period.
13. Contraindication to receive lymphodepleting chemotherapy.
14. Patients with known hypersensitivity to the active ingredients or any of the excipients of the product to be infused.

Primary outcomes:
measure: Purity of CARTemis-1
timeFrame: Immediately after infusion
measure: Maximum tolerated dose
timeFrame: Up to 30 days
measure: Infusion reactions
timeFrame: Immediately after intravenous administration of CARTemis-1
measure: Tumor lysis syndrome
timeFrame: Up to 30 days after treatment administration
measure: Serious Adverse Event
timeFrame: Up to 36 months after treatment administration
measure: Suspected Unexpected Serious Adverse Reaction
timeFrame: Up to 36 months after treatment administration
Secondary outcomes:
measure: Number of Participants with cytopenias
timeFrame: During the first 90 days after administration of CARTemis-1
measure: Number of Participants with prolonged cytopenias
timeFrame: Up to 12 months after treatment administration
measure: Duration of clinical response
timeFrame: Screening, day -5, -4, -3, +28, +56, +100 and months +4, +5, 6, +7, +8, +9, +10, +11, +12, +15 , +18, +21, +27, +30, +33, +36 or progression
measure: Overall response rate
timeFrame: 3, 6 and 12 months after CARTemis-1 infusion
measure: Time to complete remission
timeFrame: Up to 36 months after treatment administration
measure: Time to best response
timeFrame: Up to 36 months after treatment administration
measure: Negative Minimum Residual Disease Rate
timeFrame: 3, 6 and 12 months after CARTemis-1 infusion
measure: Response rate of extramedullary disease
timeFrame: 3 months after CARTemis-1 infusion
measure: Progression-free survival.
timeFrame: Up to 36 months after treatment administration
measure: Overall survival
timeFrame: Up to 36 months after treatment administration
measure: Persistence of CARTemis-1
timeFrame: Peripheral blood:days 3,7,10,14,17 (only in cohort 3 and 4),21,30,56,90,128 and 156, and months 6,9,12,15,18,24 and relapse or month 36 post-infusion; Marrow: 1,3,6,12,18 and 24 months post-infusion and in the progression or month
measure: CART cell quality
timeFrame: During the manufacturing process, at the time of infusion and at Month+1, Month+3, Month+6, Month+12, Month+18 and Month+24 post-infusion
measure: Expression of B cell maturation antigen (BCMA)
timeFrame: Screening and at the time of follow up when a relapse occurs, an average after 1 year
measure: B cell maturation antigen (BCMA) levels
timeFrame: Screening, Day -5, Day 0, +1, +3, +7 y +28 and months +3, +6, +12, +18 and +24
Other outcomes:
Locations:
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Salamanca
country: Spain
facility: Complejo asistencial universitario de Salamanca
city: Sevilla
country: Spain
facility: José Antonio Pérez Simón
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
Study officials:
affiliation: Hospitales Universitarios Virgen del Rocío
name: Jose-Antonio Perez-Simon, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: