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

Primary Purpose

Multiple Myeloma, Allogeneic Stem Cell Transplantation

Status
Not yet recruiting
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
CARTemis-1
Sponsored by
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Chimeric antigen receptor-T cell therapy, B-Cell Maturation Antigen

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. Contraindication to receive lymphodepleting chemotherapy.

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CARTemis-1

Arm Description

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

Outcomes

Primary Outcome Measures

Purity of CARTemis-1
Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused
Maximum tolerated dose
To determine the maximum tolerated dose of CarTemis-1
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.
Tumor lysis syndrome
To increase nucleic acids, potassium, and phosphate in the blood
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).
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.

Secondary Outcome Measures

Number of Participants with cytopenias
Neutropenias or thrombopenias
Number of Participants with prolonged cytopenias
Neutropenias or thrombopenias (grade ≥3) for more than 6 weeks
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.
Overall response rate
Overall response rate as assessed by criteria of the International Myeloma Working Group
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
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
Negative Minimum Residual Disease Rate
Residual amount of malignant cells in the bone marrow
Response rate of extramedullary disease
To measure of the metabolic activity of the human body by Positron Emission Tomography
Progression-free survival.
Quantification of time between administration of CARTemis-1 and disease progression or death
Overall survival
the time elapsed between the infusion of CARTemis-1 and the patient's death from any cause.
Persistence of CARTemis-1
Presence of CARTemis-1 in peripheral blood and bone marrow
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.
Expression of B cell maturation antigen (BCMA)
Genetic expression of BCMA at selection and at relapse in patients
B cell maturation antigen (BCMA) levels
Serum soluble BCMA levels pre-treatment and during treatment

Full Information

First Posted
May 2, 2023
Last Updated
October 18, 2023
Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
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1. Study Identification

Unique Protocol Identification Number
NCT05982275
Brief Title
Trial of an Investigational Drug After Rejecting the Relapse of an Allogeneic Transplant
Acronym
CARTemis-1
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: EGFR Expression as a Control Mechanism of Treatment-derived Complications
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 30, 2024 (Anticipated)
Primary Completion Date
January 31, 2028 (Anticipated)
Study Completion Date
January 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Allogeneic Stem Cell Transplantation
Keywords
Chimeric antigen receptor-T cell therapy, B-Cell Maturation Antigen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CARTemis-1
Arm Type
Experimental
Arm Description
Dose escalation sequential cohorts CARTemis-1 will be self-administered intravenously one or two days, depending on the dose administered.
Intervention Type
Genetic
Intervention Name(s)
CARTemis-1
Intervention Description
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 Measure Information:
Title
Purity of CARTemis-1
Description
Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused
Time Frame
Immediately after infusion
Title
Maximum tolerated dose
Description
To determine the maximum tolerated dose of CarTemis-1
Time Frame
Up to 30 days
Title
Infusion reactions
Description
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
Title
Tumor lysis syndrome
Description
To increase nucleic acids, potassium, and phosphate in the blood
Time Frame
Up to 30 days after treatment administration
Title
Serious Adverse Event
Description
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
Title
Suspected Unexpected Serious Adverse Reaction
Description
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 Outcome Measure Information:
Title
Number of Participants with cytopenias
Description
Neutropenias or thrombopenias
Time Frame
During the first 90 days after administration of CARTemis-1
Title
Number of Participants with prolonged cytopenias
Description
Neutropenias or thrombopenias (grade ≥3) for more than 6 weeks
Time Frame
Up to 12 months after treatment administration
Title
Duration of clinical response
Description
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
Title
Overall response rate
Description
Overall response rate as assessed by criteria of the International Myeloma Working Group
Time Frame
3, 6 and 12 months after CARTemis-1 infusion
Title
Time to complete remission
Description
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
Up to 36 months after treatment administration
Title
Time to best response
Description
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
Up to 36 months after treatment administration
Title
Negative Minimum Residual Disease Rate
Description
Residual amount of malignant cells in the bone marrow
Time Frame
3, 6 and 12 months after CARTemis-1 infusion
Title
Response rate of extramedullary disease
Description
To measure of the metabolic activity of the human body by Positron Emission Tomography
Time Frame
3 months after CARTemis-1 infusion
Title
Progression-free survival.
Description
Quantification of time between administration of CARTemis-1 and disease progression or death
Time Frame
Up to 36 months after treatment administration
Title
Overall survival
Description
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
Title
Persistence of CARTemis-1
Description
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
Title
CART cell quality
Description
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
Title
Expression of B cell maturation antigen (BCMA)
Description
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
Title
B cell maturation antigen (BCMA) levels
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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. Contraindication to receive lymphodepleting chemotherapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jose-Antonio Perez-Simon, MD-PhD
Phone
0034955013414
Email
josea.perez.simon.sspa@juntadeandalucia.es
First Name & Middle Initial & Last Name or Official Title & Degree
Clara Rosso, MD-PhD
Phone
0034955013414
Email
claram.rosso.sspa@juntadeandalucia.es
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose-Antonio Perez-Simon, MD-PhD
Organizational Affiliation
Hospitales Universitarios Virgen del Rocío
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aranzazu Bermúdez-Rodríguez, M.D. Ph.D.
Facility Name
Hospital Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Briones, MD-PhD
Facility Name
Complejo asistencial universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mª Victoria Mateos, MD-Phd
Facility Name
José Antonio Pérez Simón
City
Sevilla
ZIP/Postal Code
41011
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Antonio Pérez Simón, MD-PhD
Phone
0034955013260
Email
josea.perez.simon.sspa@juntadeandalucia.es
Facility Name
Hospital Clínico de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlos Solano Vercet, M.D. Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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