Venetoclax and Dexamethasone in translocation (11;14) positive relapsed and refractory multiple myeloma (VICTORIA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lillebaelt Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

3 Jul 2020 → ongoing

Decision date (initial)

2024-04-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512731-74-00

EudraCT number

2020-001102-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To report the efficacy of venetoclax-dexamethasone in patients with relapsed and refractory MM who are positive for t(11;14).

Conditions and MedDRA coding

multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. • Male or female, age 18 years or older
2. • A prior diagnosis of multiple myeloma
3. • At least one prior line of therapy
4. • The presence of t(11;14) by fluorescent in situ hybridization
5. • Relapsed or refractory disease defined as o progressive disease  during treatment with the last line of therapy or  within 60 days after the last line of therapy or o minimal response or better not achieved after completion of at least two cycles of the last line of therapy
6. • Measurable disease defined as any of the following: o Serum monoclonal protein ≥ 10 g/L by serum protein electrophoresis o ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis o Serum free light chain ≥ 100 mg/L and abnormal serum kappa to lambda free light chain (FLC) ratio
7. • Life expectancy of ≥ 6 months
8. • ECOG performance status ≤ 2. (Patients with performance status > 2 based solely on bone pain secondary to multiple myeloma may be eligible following approval of the sponsor);
9. • A negative serum or urine pregnancy test if the subject is a female of childbearing potential, defined as any sexually mature female who: o has not undergone a hysterectomy or bilateral oophorectomy and o has not been naturally postmenopausal for at least 24 consecutive months  A sexually mature female who stopped having menstrual cycles due to cancer therapy cannot be considered naturally postmenopausal
10. • Female patients must agree to practice highly effective method of birth control until at least 30 days after the last dose of study treatment. Highly effective method of birth control is defined as the combination of both a hormonal and a barrier method of contraception
11. • Ability to understand the purpose and risks of the study and provide signed and dated informed consent;
12. • Adequate organ function with the following laboratory results: o Absolute neutrophil count ≥ 1,000 cells/mm3 (1.0 x 109/L) o Platelet count ≥ 30,000 cells/ mm3 (30 x 109/L) (without transfusions required within 10 days prior to initiation of study treatment) o Hemoglobin ≥ 5 mmol/l; red blood cell transfusions and treatment with erythropoietin are permitted o Total Bilirubin ≤ 1.5 x upper limit of normal, except patients diagnosed with Gilbert’s syndrome that have been approved by the sponsor o Alanine transaminase ≤ 3.0 x upper limit of normal o Renal function: Estimated creatinine clearance by Cockcroft- Gault formula of ≥ 30 mL/min

Exclusion criteria 10

1. • Any somatic or psychiatric condition that in the investigator’s opinion would impose excessive risk to the patient or would adversely affect the patient’s participation in this study
2. • Severe ongoing infection that in the investigator’s opinion would impose excessive risk to the patient
3. • Known intolerance to the study treatment
4. • Pregnant or breast-feeding females
5. • Known human immunodeficiency virus or active hepatitis B or C viral infection
6. • The use of live vaccines within 30 days before initiation of study treatment
7. • Autologous stem cell transplant within 12 weeks prior to initiation of study treatment
8. • Prior allogeneic stem cell transplantation with active graft-versus-host-disease
9. • ≥ Grade 3 cardiac conduction system abnormalities unless patient has a pacemaker
10. • Cardiovascular disability status of New York Heart Association Class greater than or equal to 3

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the overall response rate (partial response or better) of the combination of Venetoclax-dexamethasone in patients with relapsed or refractory multiple myeloma

Secondary endpoints 17

1. progression-free survival
2. clinical benefit rate (minimal response or better)
3. time to next treatment
4. overall survival
5. time to response
6. duration of response
7. safety and tolerability
8. discontinuation rate
9. quality of life
10. number of serious adverse events due to infections
11. duration of hospital admissions due to infections
12. effect of PET-positivity on efficacy end-points
13. Estimation of humoral immunodeficiency of subjects at baseline by measuring serum anti-pneumococcal polysaccharide IgG, IgA, IgM antibodies
14. assessment of the relation of humoral immunodeficiency to infections
15. assessment of pneumococcal vaccination response and its relation to infections
16. estimation of Bcl-2 overexpression by immunohistochemistry
17. assessment of the relation of Bcl-2 overexpression to the efficacy of the study treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lillebaelt Hospital

Sponsor organisation

Lillebaelt Hospital

Address

Beriderbakken 4

City

Vejle

Postcode

7100

Country

Denmark

Scientific contact point

Organisation

Lillebaelt Hospital

Contact name

Agoston Gyula Szabo

Public contact point

Organisation

Lillebaelt Hospital

Contact name

Agoston Gyula Szabo

Third parties 1

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications