the tg01 study with tg01/qs-21 vaccine in patients with high-risk smouldering multiple myeloma and multiple myeloma

Conditions: Multiple Myeloma; Smoldering Multiple Myeloma

Summary: 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.


Eligibility criteria:
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.