Venetoclax, Lenalidomide and Rituximab in Patients With Relapsed/Refractory Mantle Cell Lymphoma

Relapsed Non Hodgkin Lymphoma Clinical Trial

— VALERIA  

Official title:

Venetoclax, Lenalidomide and Rituximab in Patients With Relapsed/Refractory Mantle Cell Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03505944
• Other study ID #: NLG-MCL7
• Secondary ID: 2017-001060-38
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2018
• Est. completion date: December 1, 2022

Study information

• Verified date: October 2021
• Source: Nordic Lymphoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase I/II trial, with the aim of evaluating the efficacy of venetoclax to the backbone of rituximab-lenalidomide in patients with relapsed/refractory MCL.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion criteria

• Age >18 years
• Histologically confirmed (according to the WHO 2016 classification) mantle cell lymphoma stage I-IV
• Who have received at least 1 prior rituximab-containing chemotherapy regimen, with documented relapse or disease progression following the last anti-MCL treatment OR
• Are not considered to be candidates for chemotherapy due to frailty or comorbidity
• At least 1 measurable site of disease (>1.5 cm long axis)
• WHO performance status 0 - 3
• Written informed consent.
• Female subjects of childbearing potential must (see page 52 for definition of not

fertile):

• Understand that the study medication is expected to be teratogenic
• Agree to use, and be able to comply with, highly effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea.
• All fertile women must agree to perform monthly pregnancy tests while on study medication and until 4 weeks after completion of study drug. Tests must have a minimum sensitivity of 25 mIE/ml and be medically witnessed
• Highly effective contraception include:

Implant* Levonorgestrel-releasing intrauterine system (IUS)* Medroxyprogesterone acetate depot Tubal sterilisation Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses Ovulation inhibitory progesterone-only pills (i.e., desogestrel) NB! Patients using a hormonal method, must also use a second barrier method. Sexual abstinence (if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle of the subject).

• Male subjects must
• Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
• Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
• All subjects must
• Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
• Agree not to share study medication with another person and to return all unused study drug to the investigator Exclusion criteria
• Chemotherapy or radiotherapy within 3 weeks
• Therapeutic antibodies or BTK inhibitors within 4 weeks
• Radioimmunotherapy within 10 weeks
• Major surgery within 4 weeks of inclusion in this trial.
• Previous treatment with venetoclax
• Impaired liver function: AST and ALT >3.0 × the upper normal limit (ULN) of institution's normal range; Bilirubin > 1.5 × ULN. Subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN, per discussion between the investigator and medical monitor. Elevated Bilirubin due to haemolytic anemia or caused by lymphoma, is not an exclusion criterion.
• Absolute neutrophil count (ANC) <1.0x 109, unless caused by bone marrow infiltration by lymphoma.
• Platelet count <60 x 109, unless caused by bone marrow infiltration by lymphoma.
• Creatinine clearance below 50 ml/min (Cockcroft-Gault)
• Known CNS lymphoma.
• Heart failure in NYHA stage IV or other serious CVD
• Pulmonary failure (ex chronic disease with hypoxemia)
• Active serious infections such as hepatitis B or C and HIV
• Conditions with serious immunocompromised state
• Breastfeeding women must be excluded or stop breastfeeding
• Other active malignancy.
• Psychiatric illness or condition which could interfere with the subjects' ability to understand the requirements of the study.
• Requirement of corticosteroid therapy at a dose >10 mg prednisolone/day.
• Hypersensitivity to venetoclax, lenalidomide or rituximab, or HACA against rituximab.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Relapsed Non Hodgkin Lymphoma

Intervention

Drug:
• Venetoclax
venetoclax + lenalidomide + rituximab

Locations

Country	Name	City	State
Denmark	Department of Hematology Aalborg University Hospital	Aalborg
Denmark	Department of Hematology Aarhus University Hospital	Aarhus
Denmark	Clinic of Hematology L-4241 Rigshospitalet	Copenhagen
Denmark	Department of Hematology X Odense University Hospital	Odense
Denmark	Hæmatologisk Afdeling Zeeland University Hospital, Roskilde	Roskilde
Finland	Department of Hematology Helsinki University Hospital Comprehensive Cancer Center	Helsinki
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospital	Tampere
Norway	Oslo University Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	St. Olav Hospital	Trondheim
Sweden	Department of Hematology Linköping University Hospital	Linköping
Sweden	Department of Medicine Sunderbyn Hospital	Luleå
Sweden	Skane University Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm
Sweden	Department of Oncology Norrland University Hospital	Umeå
Sweden	Uppsla Academic Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Nordic Lymphoma Group

Countries where clinical trial is conducted

Denmark,  Finland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	The primary objective is to assess the overall response rate (ORR) at 6 months with lenalidomide-venetoclax and rituximab, in patients with relapsed or refractory mantle cell lymphoma, by use of an MRD driven strategy. ORR includes complete (CR) and partial remissions (PR).	6 months