Multiple MyelomaPhase 1/2CARTemis-1NCT05982275
Trial of an Investigational Drug After Rejecting the Relapse of an Allogeneic Transplant
A Phase 1/2 study testing CARTemis-1 in people with Multiple Myeloma and Allogeneic Stem Cell Transplantation, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 5 sites in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Allogeneic Stem Cell Transplantation
- What is being tested?
- CARTemis-1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 5 sitesSpain
- Study dates
- 30 Dec 2024to 31 Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Spain5 sites
Hospital Santa Creu i Sant Pau
Barcelona, 08025
Javier Briones, MD-PhD
Complejo asistencial universitario de Salamanca
Salamanca, 37007
Mª Victoria Mateos, MD-Phd
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
Aranzazu Bermúdez-Rodríguez, M.D. Ph.D.
José Antonio Pérez Simón
Seville, 41011
José Antonio Pérez Simón, MD-PhD, 0034955013260, josea.perez.simon.sspa@juntadeandalucia.es
Hospital Clínico de Valencia
Valencia, 46010
Carlos Solano Vercet, M.D. Ph.D.
About this study
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
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.
Read the 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.
- Being tested
- CARTemis-1
- Keywords
- Chimeric antigen receptor-T cell therapy, B-Cell Maturation Antigen
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CARTemis-1Genetic
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).
| Study group | Role | What they receive |
|---|---|---|
| CARTemis-1 | Experimental | Dose escalation sequential cohorts CARTemis-1 will be self-administered intravenously one or two days, depending on the dose administered. Receives: Genetic: CARTemis-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Purity of CARTemis-1
Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused
Measured: Immediately after infusion
Maximum tolerated dose
To determine the maximum tolerated dose of CarTemis-1
Measured: 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.
Measured: Immediately after intravenous administration of CARTemis-1
Tumor lysis syndrome
To increase nucleic acids, potassium, and phosphate in the blood
Measured: 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).
Measured: 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.
Measured: Up to 36 months after treatment administration
Secondary outcomes (14)
Number of Participants with cytopenias
Neutropenias or thrombopenias
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 36 months after treatment administration
Negative Minimum Residual Disease Rate
Residual amount of malignant cells in the bone marrow
Measured: 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
Measured: 3 months after CARTemis-1 infusion
Progression-free survival.
Quantification of time between administration of CARTemis-1 and disease progression or death
Measured: 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.
Measured: Up to 36 months after treatment administration
Persistence of CARTemis-1
Presence of CARTemis-1 in peripheral blood and bone marrow
Measured: 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.
Measured: 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
Measured: 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
Measured: Screening, Day -5, Day 0, +1, +3, +7 y +28 and months +3, +6, +12, +18 and +24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2023
- Study start30 Dec 2024 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jose-Antonio Perez-Simon, MD-PhD, Principal investigator, Hospitales Universitarios Virgen del Rocío
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05982275
- Sponsor's protocol ID
- CARTemis-1
- Acronym
- CARTemis-1
- Status last verified
- May 2024
- First submitted
- 2 May 2023
- Last updated
- 14 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05982275
- Acronym / sponsor ID
- CARTemis-1 / CARTemis-1
- Keywords
- Chimeric antigen receptor-T cell therapy, B-Cell Maturation Antigen
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 30 Dec 2024 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 8 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CARTemis-1 | Experimental | Genetic: CARTemis-1Dose escalation sequential cohorts CARTemis-1 will be self-administered intravenously one or two days, depending on the dose administered. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CARTemis-1A 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). | Genetic | CARTemis-1 |
Primary outcome
Purity of CARTemis-1
Time frame: Immediately after infusion
Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused
Maximum tolerated dose
Time frame: Up to 30 days
To determine the maximum tolerated dose of CarTemis-1
Infusion reactions
Time frame: Immediately after intravenous administration of CARTemis-1
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
Time frame: Up to 30 days after treatment administration
To increase nucleic acids, potassium, and phosphate in the blood
Serious Adverse Event
Time frame: Up to 36 months after treatment administration
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
Time frame: Up to 36 months after treatment administration
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.
14 secondary outcomes
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
Expression of B cell maturation antigen (BCMA)
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
Time frame: Screening, Day -5, Day 0, +1, +3, +7 y +28 and months +3, +6, +12, +18 and +24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
- Individual participant dataSharing planned: Yes. The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jose-Antonio Perez-Simon, MD-PhD principal investigator
Hospitales Universitarios Virgen del Rocío
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CARTemis-1 in people with Multiple Myeloma and Allogeneic Stem Cell Transplantation, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 5 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jose-Antonio Perez-Simon, MD-PhD (0034955013414, josea.perez.simon.sspa@juntadeandalucia.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Purity of CARTemis-1 (time frame: Immediately after infusion). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.