The TG01 Study With TG01/QS-21 Vaccine in Patients With High-risk Smouldering Multiple Myeloma and Multiple Myeloma

Trial Title: The TG01 Study With TG01/QS-21 Vaccine in Patients With High-risk Smouldering Multiple Myeloma and Multiple Myeloma

NCT ID: NCT05841550

Condition: Multiple Myeloma
Smoldering Multiple Myeloma

Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: TG01
Description: All participants will receive the same treatment as described under arm
Arm group label: TG01

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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Oslo Myeloma Center

Address:
City: Oslo
Zip: 0450
Country: Norway

Status: Recruiting

Contact:
Last name: Fredrik B Schjesvold, MD, PhD

Phone: 996 97 796

Phone ext: 0047
Email: fredrikschjesvold@gmail.com

Contact backup:
Last name: Hanne M Norseth, MD

Phone: 92847595

Phone ext: 0047
Email: h.m.norseth@gmail.com

Start date: May 19, 2023

Completion date: May 19, 2035

Lead sponsor:
Agency: Oslo University Hospital
Agency class: Other

Collaborator:
Agency: Targovax ASA
Agency class: Industry

Source: Oslo University Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05841550