Multiple Myeloma Clinical Trial
Official title:
A Phase 1/Phase 2 Study to Investigate Safety, Tolerability and Efficacy With TG01/QS-21 Vaccine Administration in Patients With Confirmed KRAS or NRAS Codon 12/13 Mutation and High-risk Smoldering Multiple Myeloma or Multiple Myeloma and Evidence of Measurable Disease ≥ 1 Line of Treatment
The goal of this clinical trial is to test the safety, tolerability, and efficacy of TG01 vaccination in patients with KRAS or NRAS mutation on codon 12/13 mutation who has multiple myeloma or high-risk smoldering multiple myeloma. The main question it aims to answer are: Is TG01/QS-21 vaccination safe and tolerable for this patient group? Is TG01/QS-21 vaccination treatment efficient in this group in terms of increased overall response rate, overall survival rate, progression-free survival, and time til next treatment? Is there an immunological response to the vaccine? Participants will be given TG01/QS-21 vaccination treatment. Treatment consists of 12 doses of TG01/QS-21 vaccine given every two weeks in the first 12 weeks, followed by every eight weeks until week 52.
Status | Recruiting |
Enrollment | 20 |
Est. completion date | May 19, 2035 |
Est. primary completion date | May 19, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Male or female patients = 18 years of age - RAS mutation (KRAS/NRAS codon 12/13 mutation) detected on archival or fresh bone marrow material with VariantPlex Myeloid Panel - Confirmed diagnosis of high-risk smoldering multiple myeloma (SMM) according to IMWG criteria (30) and high-risk criteria as listed up below OR confirmed diagnosis of multiple myeloma (MM) according to IMWG criteria and measurable disease following = 1 line of treatment - In patients with high-risk SMM at least 2 of 3 following abnormalities, based on laboratory data obtained at screening must be fulfilled: 1. Serum M-protein >20 g/L. 2. Serum involved/uninvolved FLC ratio >20. 3. BMPC >20%. OR presence of =10% BMPC and at least one of the following based on laboratory data obtained at screening: - Serum M-protein =30 g/L (If IgA, IgA =20g/L) - Serum involved/uninvolved FLC ratio =8 (but <100) - Abnormal PC immunophenotype (=95% of BMPCs are clonal) and reduction of =1uninvolved Ig isotype (Only IgG, IgA and IgM will be considered) - Progressive increase in Serum M-protein level (evolving type of SMM) defined as an increase of Serum M-protein =10% in the last 12 months before enrolment in the study. This increase must be consistent from one to another sample (i.e., no decrease observed between 2 increased Serum M-protein values) - Both high-risk SMM and MM patients must have evidence of measurable disease in accordance with IMWG criteria - If patient with MM was eligible for ASCT, ASCT must have been performed, and patients cannot be enrolled until 3 months after ASCT - Patient should not be expected to require immediate, subsequent line of treatment for at least 2 months - Patient has not had reduction of clonal plasma cell markers for last two cycles (last two months if off treatment). If a patient had no reduction during the last two cycles of induction before ASCT, the patient can be enrolled, provided 3 months after ASCT - Following ASCT, the patient cannot be enrolled without having tried lenalidomide maintenance given at standard doses for at least two cycles, if the clonal markers had a reduction during the last 2 cycles of induction treatment. Lenalidomide will be stopped when entering the study - ECOG performance status 0-1 - Female patients of child-bearing potential (FCBP) must have negative serum pregnancy test at Screening and agree to use a highly effective method of contraception during treatment and for 3 months following last dose of drug. - Male patients must use an effective barrier method of contraception during treatment and for 3 months following the last dose if sexually active with a FCBP. - Ability to provide written informed consent and can understand and comply with the requirements of the study Exclusion Criteria: - Pregnant or lactating women or women without a pregnancy test at baseline (postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential) - Medical conditions such as but not limited to: 1. Any uncontrolled infection 2. Uncontrolled cardiac failure classification III or IV (NYHA) 3. Uncontrolled systemic and gastro-intestinal inflammatory conditions 4. History of adverse reactions to vaccines - Active malignancy with worse prognosis than multiple myeloma - Likely to require treatment intervention for multiple myeloma within two months of start of treatment with TG01/QS-21 - Known history of positive tests for HIV/AIDS, hepatitis B or C - Planned to receive yellow fever or other live (attenuated) vaccines during the course of study - Known hypersensitivity to QS-21. - Only participants who are able to consent will be included in the study. |
Country | Name | City | State |
---|---|---|---|
Norway | Oslo Myeloma Center | Oslo |
Lead Sponsor | Collaborator |
---|---|
Oslo University Hospital | Targovax ASA |
Norway,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of participants with adverse events (AEs) | An Adverse Event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Baseline until 30 days after last dose of study drug, up to approximately 3 years | |
Primary | Percentage of participants discontinuing treatment secondary to treatment-related adverse events | Percentage of participants discontinuing treatment secondary to treatment-related adverse events | Up to approximately 3 years | |
Secondary | Number of patients with Progression Free Survival (PFS) | defined as the time from study treatment start to disease progression for every patient | Baseline to 11 years | |
Secondary | Concentration of TG01-specific T-cell specific cytokine production | The immune response to TG01 will be measured by IFNg/TNFa ELISPOT or FluoroSpot quantifying the TG01 T-cell specific cytokine production. A positive immune response will be defined as a 2-fold higher mean spot number in experimental wells (with vaccine peptides) compared to control wells (medium) | Baseline until end of study, assessed up to 11 years | |
Secondary | Overall response rate per patient | The proportion of patients who achieve partial response (PR) or better following at least one dose of study treatment | Baseline to approximately 3 years | |
Secondary | Overall Survival (OS) per patient | The OS rate of patients receiving 1 or more study treatments | Baseline until the end of study, assessed up to 11 years | |
Secondary | Time to next treatment (TTNT) per patient | defined as the time between the start date of the current treatment line and the start date of the next treatment line | Baseline until the end of study, assessed up to 11 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05027594 -
Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02412878 -
Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
|
Phase 3 | |
Completed |
NCT01947140 -
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05971056 -
Providing Cancer Care Closer to Home for Patients With Multiple Myeloma
|
N/A | |
Recruiting |
NCT05243797 -
Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation
|
Phase 3 | |
Active, not recruiting |
NCT04555551 -
MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT05618041 -
The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies
|
N/A | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Recruiting |
NCT03412877 -
Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer
|
Phase 2 | |
Completed |
NCT02916979 -
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
|
Phase 1 | |
Recruiting |
NCT03570983 -
A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion
|
Phase 2 | |
Terminated |
NCT03399448 -
NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)
|
Phase 1 | |
Completed |
NCT03665155 -
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
|
Phase 1/Phase 2 | |
Completed |
NCT02812706 -
Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT05024045 -
Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
|
Phase 1 | |
Active, not recruiting |
NCT03989414 -
A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT03792763 -
Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients
|
Phase 2 | |
Withdrawn |
NCT03608501 -
A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation
|
Phase 2 | |
Recruiting |
NCT04537442 -
Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02546167 -
CART-BCMA Cells for Multiple Myeloma
|
Phase 1 |