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

Overview

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.

Interventions

• Genetic CARTemis-1
  A dose escalation design will be applied in successive patient cohorts until identification of Dose Limiting Toxicity (maximum dose: 6x10\^6 CAR-T/kg divided over 2 days).

Primary outcome measures

• Purity of CARTemis-1 [Time frame: Immediately after infusion]
• Maximum tolerated dose [Time frame: Up to 30 days]
• Infusion reactions [Time frame: Immediately after intravenous administration of CARTemis-1]
• Tumor lysis syndrome [Time frame: Up to 30 days after treatment administration]
• Serious Adverse Event [Time frame: Up to 36 months after treatment administration]
• Suspected Unexpected Serious Adverse Reaction [Time frame: Up to 36 months after treatment administration]

Secondary outcome measures (12)

• Number of Participants with cytopenias [Time frame: During the first 90 days after administration of CARTemis-1]
• Number of Participants with prolonged cytopenias [Time frame: Up to 12 months after treatment administration]
• Duration of clinical response [Time frame: 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]
• Overall response rate [Time frame: 3, 6 and 12 months after CARTemis-1 infusion]
• Time to complete remission [Time frame: Up to 36 months after treatment administration]
• Time to best response [Time frame: Up to 36 months after treatment administration]
• Negative Minimum Residual Disease Rate [Time frame: 3, 6 and 12 months after CARTemis-1 infusion]
• Response rate of extramedullary disease [Time frame: 3 months after CARTemis-1 infusion]
• Progression-free survival. [Time frame: Up to 36 months after treatment administration]
• Overall survival [Time frame: Up to 36 months after treatment administration]
• Persistence of CARTemis-1 [Time frame: 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]
• CART cell quality [Time frame: 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]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Active systemic immunosuppressive treatment
• Patients who have previously received treatment with CAR-T Anti-BCMA.
• Absolute lymphocyte count <0.2x109/L
• Previous neoplasm, except if it has been in complete remission >3 years, with the exception of skin carcinoma (non-melanoma)
• Active infection requiring treatment.
• Active HIV, hepatitis B virus or hepatitis C virus infection.
• Uncontrolled medical illness.
• 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).
• Previous diagnosis of symptomatic amyloid light chain or primary amyloidosis or POEMS Syndrome.
• Pregnant or lactating women.
• Women of childbearing age, unable or unwilling to use highly effective contraceptive methods.
• 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.
• Contraindication to receive lymphodepleting chemotherapy.
• Patients with known hypersensitivity to the active ingredients or any of the excipients of the product to be infused.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 5 centers

• Hospital Universitario Marques de Valdecilla — Santander
• Hospital Santa Creu i Sant Pau — Barcelona
• Complejo asistencial universitario de Salamanca — Salamanca
• José Antonio Pérez Simón — Seville
• Hospital Clínico de Valencia — Valencia

Identifiers

NCT: NCT05982275 · CARTemis-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗