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

Phase 2Not Yet RecruitingNCT05982275

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla25 enrolled

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma Allogeneic Stem Cell Transplantation

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Purity of CARTemis-1

Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused

Time frame: Immediately after infusion

Maximum tolerated dose

To determine the maximum tolerated dose of CarTemis-1

Time frame: 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.

Time frame: Immediately after intravenous administration of CARTemis-1

Tumor lysis syndrome

To increase nucleic acids, potassium, and phosphate in the blood

Time frame: 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).

Time frame: 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.

Time frame: Up to 36 months after treatment administration

Secondary Outcomes

Number of Participants with cytopenias

Neutropenias or thrombopenias

Time frame: 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

Time frame: 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.

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

Overall response rate as assessed by criteria of the International Myeloma Working Group

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

Residual amount of malignant cells in the bone marrow

Time frame: 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

Time frame: 3 months after CARTemis-1 infusion

Progression-free survival.

Quantification of time between administration of CARTemis-1 and disease progression or death

Time frame: 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.

Time frame: Up to 36 months after treatment administration

Persistence of CARTemis-1

Presence of CARTemis-1 in peripheral blood and bone marrow

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

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.

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

Expression of B cell maturation antigen (BCMA)

Genetic expression of BCMA at selection and at relapse in patients

Time frame: 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

Time frame: Screening, Day -5, Day 0, +1, +3, +7 y +28 and months +3, +6, +12, +18 and +24

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

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts