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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05951959




Registration number
NCT05951959
Ethics application status
Date submitted
5/06/2023
Date registered
19/07/2023

Titles & IDs
Public title
A Study of Acalabrutinib Plus Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma
Scientific title
A Multicentre, Phase II, Open-label Study to Evaluate the Efficacy of Acalabrutinib in Combination With Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma (TrAVeRse)
Secondary ID [1] 0 0
2023-505205-16-00
Secondary ID [2] 0 0
D822GC00001
Universal Trial Number (UTN)
Trial acronym
TrAVeRse
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mantle Cell Lymphoma (MCL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Acalabrutinib
Treatment: Drugs - Venetoclax
Treatment: Drugs - Rituximab

Experimental: Acalabrutinib + Venetoclax + Rituximab - Acalabrutinib + Venetoclax + Rituximab (AVR)


Treatment: Drugs: Acalabrutinib
Investigational Product

Treatment: Drugs: Venetoclax
Investigator Product

Treatment: Drugs: Rituximab
Investigator Product
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MRD-negative CR rate
Timepoint [1] 0 0
At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
Secondary outcome [1] 0 0
MRD-negative CR rate
Timepoint [1] 0 0
Up to approximately 67 months
Secondary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
Up to approximately 67 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR)
Timepoint [3] 0 0
At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
Secondary outcome [4] 0 0
Complete Response (CR) rate
Timepoint [4] 0 0
Up to approximately 67 months
Secondary outcome [5] 0 0
Complete Response (CR) rate
Timepoint [5] 0 0
At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
Secondary outcome [6] 0 0
Duration of Response (DoR)
Timepoint [6] 0 0
Up to approximately 67 months
Secondary outcome [7] 0 0
Time to Next Treatment (TTNT)
Timepoint [7] 0 0
Up to approximately 67 months
Secondary outcome [8] 0 0
Progression-free Survival (PFS)
Timepoint [8] 0 0
Up to approximately 67 months
Secondary outcome [9] 0 0
Event Free Survival (EFS)
Timepoint [9] 0 0
Up to approximately 67 months
Secondary outcome [10] 0 0
Overall Survival (OS)
Timepoint [10] 0 0
Up to approximately 67 months
Secondary outcome [11] 0 0
Post randomization time to first occurrence of relapse or death, EFS and TTNT in continued acalabrutinib arm compared to observation arm.
Timepoint [11] 0 0
Yearly from Cycle 15 (each cycle is 28 days) Day 1, until 3 years after randomization
Secondary outcome [12] 0 0
Number of participants with any Adverse Events (AE), Serious Adverse Events (SAE), Adverse Event of Special Interest (AESI) and AEs leading to study treatment discontinuation or dose modification.
Timepoint [12] 0 0
Up to approximately 67 months

Eligibility
Key inclusion criteria
Age

1. Participant must be = 18 years or the legal age of consent in the jurisdiction in which the study is taking place, whichever is greater, at the time of signing the informed consent.

Type of Participant and Disease Characteristics
2. Histologically documented MCL based on criteria established by the World Health Organization with documentation of chromosomal translocation t(11;14) (q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (e.g., CD5, CD19, CD20 or PAX5).
3. Clinical Stage II, III, or IV by Ann Arbor Classification and requiring systemic treatment in the opinion of the treating clinician.
4. At least 1 measurable site of disease per Lugano Classification for NHL (Appendix K). The site of disease must be > 1.5 cm in the long axis regardless of short axis measurement or > 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions, as assessed by diagnostic quality CT (MRI may be used for participants who are either allergic to CT contrast media or have renal insufficiency that per institutional guidelines restricts the use of CT contrast media).

OR Participant with leukemic non-nodal MCL presentation with splenomegaly (spleen >13 cm in length cranial to caudal) and Bone Marrow (BM) involvement.
5. Eastern Cooperative Oncology Group PS of 0, 1, or 2 and ECOG PS of 3 if poor PS is due to lymphoma.
6. Confirmed availability of sufficient FFPE tumour samples for central laboratory genomic profiling, including TP53 and clone identification for MRD testing per clonoSEQ® assay. Participants with leukemic non-nodal MCL may be enrolled with available BM tissue. For non-nodal leukaemic MCL participants and when nodal or extranodal tissue is not easily accessible and an invasive biopsy will cause a significant risk to the participant, the participant can be enrolled without a tissue biopsy if MCL BM involvement is confirmed by a BM biopsy and sufficient BM biopsy and aspirate provided for TP53 testing, tumour profiling and clone identification for MRD testing.
7. Adequate organ and bone marrow function.

Sex and Contraceptive/Barrier Requirements 8 Male and/or female Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

1. Male participants:

- Male participants with a female partner of child-bearing potential should use a condom from enrolment, throughout the study until 90 days following the last dose of venetoclax or rituximab, whichever is longer.
* For non-pregnant potentially childbearing partners, contraception recommendations should also be considered. A male participant must agree to refrain from sperm donation throughout the study until 90 days following the last dose of venetoclax or rituximab, whichever is longer.
2. Female participants:

* Women of childbearing potential must have negative serum pregnancy test result prior to the start of study intervention (Cycle 1 Day 1) and agree to abstain from breastfeeding during study participation and at least 12 months after the last drug administration.
* Female participants of childbearing potential who are sexually active with a nonsterilized male partner must agree to use at least one highly effective form of birth control from enrolment, throughout the study and at least 2 days after the last dose of acalabrutinib, at least 6 months after the last dose of venetoclax, and at least 12 months after the last dose of rituximab, whichever is longer.

Informed Consent 9 Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Informed consent may be given either by the participant or their legally authorised representative.

10 Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical Conditions

1. Active CNS involvement by lymphoma or leptomeningeal disease
2. Current or previous active malignancies requiring anticancer therapy except:

- adequately treated basal cell or squamous cell skin cancer

- in situ cancer

- history of cancer with no evidence of recurrence for = 2 years before enrolment

- local radiotherapy with a field that does not overlap with sites of current MCL disease and given at least 3 months prior to the screening PET-CT scan and the participant had recovered from any associated toxicity.

- anti-hormonal therapies are permitted after discussion with the sponsor's medical monitor
3. Participants for whom the goal of therapy is tumour debulking before ASCT
4. Any severe or life-threatening illness, medical condition (e.g., uncontrolled hypertension, bleeding diathesis), or organ system dysfunction which, in the investigator' opinion, could compromise the participant safety, interfere with the absorption or metabolism of study intervention (acalabrutinib, rituximab, venetoclax) or put the study outcomes at undue risk
5. Clinically significant cardiovascular disease such as uncontrolled or untreated symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, or QTc > 480 msec at screening. Exception: Participants with controlled, asymptomatic atrial fibrillation during screening may enroll.
6. Any active uncontrolled infection (bacterial, viral, fungal, or other infection including tuberculosis), defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment, which in the investigator's opinion makes it undesirable or pose a safety risk for the participant to participate in the study.
7. HIV infection. As per standard of care, results of HIV serology should be known prior to start of study intervention. In the acute situation, registration may occur without the results of the HIV serology but must be available prior to start of study intervention

Excluded Participants: Participants with active HIV infection (i.e., with detectable viral load by PCR) are excluded.

Included Participants: HIV-positive participants receiving anti-retroviral treatment with undetectable viral load by PCR may be enrolled following discussion with the participant's HIV physician and the sponsor medical monitor. Potential interactions between anti-retroviral medications and study interventions should be considered.
8. Serologic status reflecting active hepatitis B or C. As per standard of care, results of hepatitis serology should be known prior to start of study intervention. In the acute situation, enrolment may occur without the results of the hepatitis serology but must be available prior to start of study intervention.

1. Participants who are HBsAg positive or HBV-DNA PCR positive will not be eligible. Participants who are anti-HBc IgG antibody positive and who are HBsAg negative will need to have a negative PCR result before enrolment. Participants who have protective titres of HBsAb after vaccination will be eligible.
2. Participants who are hepatitis C antibody positive and are HCV-PCR positive will not be eligible.
9. History or ongoing confirmed progressive multifocal leukoencephalopathy.
10. History of stroke or intracranial haemorrhage within 6 months prior to the first dose of study intervention (Cycle 1 Day 1).
11. Uncontrolled autoimmune haemolytic anaemia or idiopathic thrombocytopenic purpura.
12. Active bleeding from a gastrointestinal ulcer, except incidental finding identified on endoscopy that is attributable to MCL
13. Participants with a known hypersensitivity to acalabrutinib, venetoclax, or rituximab or any of the excipients of the product.
14. Known allergy to uric acid lowering agents (e.g., xanthine oxidase inhibitors or rasburicase)
15. Severe prior reactions to monoclonal antibodies
16. Known glucose-6-phosphate dehydrogenase deficiency
17. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass or inability to swallow the formulated product (tablets).
18. Currently pregnant (confirmed with positive pregnancy test) or breast feeding

Prior/Concomitant Therapy
19. Any prior therapies for the treatment of MCL with the exception of involved site radiotherapy given at least 3 months prior to screening PET-CT scan and where the radiotherapy field does not overlap areas of current disease activity.
20. Requiring continued treatment with a strong CYP3A4 inhibitor/inducer or its use within 7 days prior to the first dose (Cycle 1 Day 1) of acalabrutinib or venetoclax 21 Requiring continued anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon). Exceptions are DOACs rivaroxaban, apixaban, edoxaban and dabigatran

22 Requiring ongoing immunosuppressive therapy, including systemic or enteric corticosteroids except:

* Topical or inhaled corticosteroids or low-dose oral steroids (= 20 mg of prednisone or equivalent per day) as a therapy for comorbid conditions
* Short courses of glucocorticoids in excess of 20 mg prednisone for no more than 14 days for comorbid conditions.
* Systemic use of corticosteroids as a pre-phase to control MCL manifestations (up to approximately 100 mg prednisolone or equivalent daily) for up to 10 days.

23 Received major surgery (excluding placement of vascular access or for diagnosis) within 28 days of first dose of study intervention (Cycle 1 Day 1) 24 Receipt of live, attenuated vaccine within 28 days before the first dose of study intervention (Cycle 1 Day 1).

See Section 6.9, for lists of prohibited (Table 15) and restricted (Table 16) concomitant medications.

Prior/Concurrent Clinical Study Experience 25 Concurrent participation in another therapeutic clinical trial or participation in another clinical study with an investigational product or investigational medicinal device within 30 days prior to first dose of study treatment (Cycle 1 Day 1).

Other Exclusions 26 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

27 Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.

28 Previous enrolment in the present study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
7/07/2028
Actual
Sample size
Target
Accrual to date
Final
108
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Heidelberg
Recruitment hospital [2] 0 0
Research Site - Kogarah
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment hospital [4] 0 0
Research Site - Sydney
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
NSW 2217 - Kogarah
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment postcode(s) [4] 0 0
2109 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Brazil
State/province [6] 0 0
Porto Alegre
Country [7] 0 0
Brazil
State/province [7] 0 0
Rio de Janeiro
Country [8] 0 0
Brazil
State/province [8] 0 0
Sao Paulo
Country [9] 0 0
Brazil
State/province [9] 0 0
São Paulo
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
British Columbia
Country [12] 0 0
Canada
State/province [12] 0 0
Nova Scotia
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Poland
State/province [15] 0 0
Gdynia
Country [16] 0 0
Poland
State/province [16] 0 0
Kraków
Country [17] 0 0
Poland
State/province [17] 0 0
Warszawa
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Birmingham
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Gloucester
Country [21] 0 0
United Kingdom
State/province [21] 0 0
London
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Norwich
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Nottingham
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05951959