CARTemis-1: Trial of an Investigational Drug After Rejecting the Rejection of an Allogeneic Transplant
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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
Arms and Interventions
| 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).
|
Outcome Measures
Primary Outcome Measures
- Purity of CARTemis-1 [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 [Up to 30 days]
To determine the maximum tolerated dose of CarTemis-1
- Infusion reactions [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 [Up to 30 days after treatment administration]
To increase nucleic acids, potassium, and phosphate in the blood
- Serious Adverse Event [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 [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.
Secondary Outcome Measures
- Number of Participants with cytopenias [During the first 90 days after administration of CARTemis-1]
Neutropenias or thrombopenias
- Number of Participants with prolonged cytopenias [Up to 12 months after treatment administration]
Neutropenias or thrombopenias (grade ≥3) for more than 6 weeks
- 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]
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 [3, 6 and 12 months after CARTemis-1 infusion]
Overall response rate as assessed by criteria of the International Myeloma Working Group
- Time to complete remission [Up to 36 months after treatment administration]
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 [Up to 36 months after treatment administration]
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 [3, 6 and 12 months after CARTemis-1 infusion]
Residual amount of malignant cells in the bone marrow
- Response rate of extramedullary disease [3 months after CARTemis-1 infusion]
To measure of the metabolic activity of the human body by Positron Emission Tomography
- Progression-free survival. [Up to 36 months after treatment administration]
Quantification of time between administration of CARTemis-1 and disease progression or death
- Overall survival [Up to 36 months after treatment administration]
the time elapsed between the infusion of CARTemis-1 and the patient's death from any cause.
- Persistence of CARTemis-1 [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]
Presence of CARTemis-1 in peripheral blood and bone marrow
- CART 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]
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) [Screening and at the time of follow up when a relapse occurs, an average after 1 year]
Genetic expression of BCMA at selection and at relapse in patients
- B cell maturation antigen (BCMA) levels [Screening, Day -5, Day 0, +1, +3, +7 y +28 and months +3, +6, +12, +18 and +24]
Serum soluble BCMA levels pre-treatment and during treatment
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients > 18 years old with a diagnosis of post-allogeneic transplant relapse multiple myeloma.
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Measurable disease at the time of screening
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Previous treatment with ≥2 lines before and/or after allogeneic transplant.
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Patients who are not receiving immunosuppressants at least 1 month before inclusion and who do not have active graft-versus-host disease.
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Eastern Cooperative Oncology Group functional status from 0 to 1.
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Life expectancy greater than 3 months (at the time of screening)
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Patients who give their consent by signing the Informed Consent document.
Exclusion Criteria:
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Active systemic immunosuppressive treatment
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Patients who have previously received treatment with CAR-T Anti-BCMA.
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Absolute lymphocyte count <0.2x109/L
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Previous neoplasm, except if it has been in complete remission >3 years, with the exception of skin carcinoma (non-melanoma)
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Active infection requiring treatment.
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Active HIV, hepatitis B virus or hepatitis C virus infection.
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Uncontrolled medical illness.
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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).
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Previous diagnosis of symptomatic amyloid light chain or primary amyloidosis or POEMS Syndrome.
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Pregnant or lactating women.
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Women of childbearing age, unable or unwilling to use highly effective contraceptive methods.
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Men who cannot or do not wish to use highly effective contraceptive methods.
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Contraindication to receive lymphodepleting chemotherapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitario Marques de Valdecilla | Santander | Cantabria | Spain | 39008 |
| 2 | Hospital Santa Creu i Sant Pau | Barcelona | Spain | 08025 | |
| 3 | Complejo asistencial universitario de Salamanca | Salamanca | Spain | 37007 | |
| 4 | José Antonio Pérez Simón | Sevilla | Spain | 41011 | |
| 5 | Hospital Clínico de Valencia | Valencia | Spain | 46010 |
Sponsors and Collaborators
- 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 Documents (Full-Text)
None provided.More Information
Publications
None provided.- CARTemis-1