Trial of an Investigational Drug After Rejecting the Relapse of an Allogeneic Transplant

NCT05982275 | Not Yet Recruiting Phase 1

• 1 other identifier: CARTemis-1
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 5

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.

Conditions

Multiple Myeloma; Allogeneic Stem Cell Transplantation

Keywords

Chimeric antigen receptor-T cell therapy; B-Cell Maturation Antigen

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (14)

• Number of Participants with cytopenias

  During the first 90 days after administration of CARTemis-1

• Number of Participants with prolonged cytopenias

  Up to 12 months after treatment administration

• Duration of clinical response

  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

  3, 6 and 12 months after CARTemis-1 infusion

• Time to complete remission

  Up to 36 months after treatment administration

Study Arms (1)

CARTemis-1

EXPERIMENTAL

Dose escalation sequential cohorts CARTemis-1 will be self-administered intravenously one or two days, depending on the dose administered.

Genetic: CARTemis-1

Interventions

CARTemis-1 GENETIC

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).

CARTemis-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead

Study Sites (5)

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Complejo asistencial universitario de Salamanca

Salamanca, 37007, Spain

Location

José Antonio Pérez Simón

Seville, 41011, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jose-Antonio Perez-Simon, MD-PhD

  Hospitales Universitarios Virgen del Rocío

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jose-Antonio Perez-Simon, MD-PhD

CONTACT

0034955013414; josea.perez.simon.sspa@juntadeandalucia.es

Clara Rosso, MD-PhD

CONTACT

0034955013414; claram.rosso.sspa@juntadeandalucia.es

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: August 8, 2023
• Study Start: December 30, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Along the study
• Access Criteria: Direct collaborators within the study

Locations

ES (5)