Trial of an Investigational Drug After Rejecting the Relapse of an Allogeneic Transplant (CARTemis-1)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma; Allogeneic Stem Cell Transplantation
• Intervention / Treatment: Genetic: CARTemis-1

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.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jose-Antonio Perez-Simon, MD-PhD; Phone Number: 0034955013414; Email: josea.perez.simon.sspa@juntadeandalucia.es
• Study Contact Backup: Name: Clara Rosso, MD-PhD; Phone Number: 0034955013414; Email: claram.rosso.sspa@juntadeandalucia.es

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Hospital Santa Creu i Sant Pau
    • Contact: Javier Briones, MD-PhD
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca
    • Contact: Mª Victoria Mateos, MD-Phd
  • Sevilla, Spain, 41011
    • José Antonio Pérez Simón
    • Contact: José Antonio Pérez Simón, MD-PhD; Phone Number: 0034955013260; Email: josea.perez.simon.sspa@juntadeandalucia.es
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
    • Contact: Carlos Solano Vercet, M.D. Ph.D.
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
      • Contact: Aranzazu Bermúdez-Rodríguez, M.D. Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CARTemis-1; Dose escalation sequential cohorts CARTemis-1 will be self-administered intravenously one or two days, depending on the dose administered.	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Purity of CARTemis-1	Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused	Immediately after infusion
Maximum tolerated dose	To determine the maximum tolerated dose of CarTemis-1	Up to 30 days
Infusion reactions	To appearance of any of the following symptoms after intravenous administration of CARTemis-1: cardiac events, chills, dyspnea, fatigue, sudden hypertension, hypotension, nausea, pain, fever, skin rash, and urticaria.	Immediately after intravenous administration of CARTemis-1
Tumor lysis syndrome	To increase nucleic acids, potassium, and phosphate in the blood	Up to 30 days after treatment administration
Serious Adverse Event	Type, incidence, severity (graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0), timing, intensity, and relatedness of adverse events).	Up to 36 months after treatment administration
Suspected Unexpected Serious Adverse Reaction	Describe the adverse event that occurs in a clinical trial subject, which is assessed by the sponsor and or study investigator as being unexpected, serious and as having a reasonable possibility of a causal relationship with the study drug.	Up to 36 months after treatment administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with cytopenias	Neutropenias or thrombopenias	During the first 90 days after administration of CARTemis-1
Number of Participants with prolonged cytopenias	Neutropenias or thrombopenias (grade ≥3) for more than 6 weeks	Up to 12 months after treatment administration
Duration of clinical response	Duration of clinical response as assessed by Urinalysis (immunofixation, proteinuria and 24-h urine proteinogram), Blood tests (total immunoglobulin A, G and M, immunofixation and proteinogram (M component) in serum; serum free light chains), Bone Marrow Aspirate and Positron Emission Tomography.	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	Overall response rate as assessed by criteria of the International Myeloma Working Group	3, 6 and 12 months after CARTemis-1 infusion
Time to complete remission	Duration of clinical response as assessed by Urinalysis (immunofixation, proteinuria and 24-h urine proteinogram), Blood tests (total immunoglobulin A, G and M, immunofixation and proteinogram (M component) in serum; serum free light chains), Bone Marrow Aspirate and Positron Emission Tomography	Up to 36 months after treatment administration
Time to best response	Duration of clinical response as assessed by Urinalysis (immunofixation, proteinuria and 24-h urine proteinogram), Blood tests (total immunoglobulin A, G and M, immunofixation and proteinogram (M component) in serum; serum free light chains), Bone Marrow Aspirate and Positron Emission Tomography	Up to 36 months after treatment administration
Negative Minimum Residual Disease Rate	Residual amount of malignant cells in the bone marrow	3, 6 and 12 months after CARTemis-1 infusion
Response rate of extramedullary disease	To measure of the metabolic activity of the human body by Positron Emission Tomography	3 months after CARTemis-1 infusion
Progression-free survival.	Quantification of time between administration of CARTemis-1 and disease progression or death	Up to 36 months after treatment administration
Overall survival	the time elapsed between the infusion of CARTemis-1 and the patient's death from any cause.	Up to 36 months after treatment administration
Persistence of CARTemis-1	Presence of CARTemis-1 in peripheral blood and bone marrow	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	Evaluation of the biological characteristics of CARTemis-1 performed by flow cytometry to identify the optimal time of expansion as well as to study the dynamics of CAR T cells during the manufacturing process and how the manufacturing impacts on CAR T cell features and, therefore, CAR T cell quality.	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
Expression of B cell maturation antigen (BCMA)	Genetic expression of BCMA at selection and at relapse in patients	Screening and at the time of follow up when a relapse occurs, an average after 1 year
B cell maturation antigen (BCMA) levels	Serum soluble BCMA levels pre-treatment and during treatment	Screening, Day -5, Day 0, +1, +3, +7 y +28 and months +3, +6, +12, +18 and +24

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: Jose-Antonio Perez-Simon, MD-PhD, Hospitales Universitarios Virgen del Rocío

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: August 1, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: B-Cell Maturation Antigen; Chimeric antigen receptor-T cell therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CARTemis-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.
• IPD Sharing Time Frame: Along the study
• IPD Sharing Access Criteria: Direct collaborators within the study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No