This study has been transitioned to CTIS with ID 2023-507695-52-00 check the CTIS register for the current data. To compare progression-free survival (PFS) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Assessed by independent review committee (IRC)
• PFS per Lugano criteria
Secondary outcome
Assessed by both investigator assessment and IRC
• Overall response rate (ORR) per Lugano criteria
• Duration of response (DOR) per Lugano criteria
Assessed by investigator assessment:
• PFS per Lugano criteria
• OS
• EFS
• TTF
• TTNT
• PFS2
Incidence and severity of serious adverse events (SAEs), adverse events
(AEs), deaths, and clinical laboratory abnormalities per Common
Terminology
Criteria for Adverse Events (CTCAE v5.0)
• Comparative tolerability: proportion of time with high side-effect
burden
• TTW of MCL-related symptoms
Background summary
This is a global, multicentre, open-label, randomized study evaluating the
differences in efficacy, safety and tolerability of LOXO-305, a non-covalent
BTK inhibitor as monotherapy (Arm A) compared to investigator choice of
covalent BTK inhibitor monotherapy (Arm B, treatment with ibrutinib,
acalabrutinib, or zanubrutinib) in patients with previously treated mantle cell
lymphoma, who hasn*t received a BTK-inhibitor treatment before. The preliminary
results evaluating LOXO-305 have demonstrated robust and durable anti-tumour
activity, response rates and duration of therapy that compare favourably to
standard of care therapies. These results support the current comparative
trial.
Study objective
This study has been transitioned to CTIS with ID 2023-507695-52-00 check the CTIS register for the current data.
To compare progression-free survival (PFS) of LOXO-305 as monotherapy (Arm A)
to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in
patients with previously treated mantle cell lymphoma (MCL).
Study design
BRUIN MCL-321 is a Phase 3, global, multicenter, randomized open label study
comparing LOXO-305 as continuous monotherapy (Arm A) with investigator*s choice
of BTK inhibitor monotherapy (Arm B) in patients with previously treated MCL.
Intervention
Subjects will be randomized 1:1 to Arm A (LOXO-305) versus Arm B
(investigator's choice of BTK inhibitor).
Subjects enrolled in Arm A receive 200mg LOXO-305 each day and subjects
enrolled in Arm B receive 560mg ibrutinib each day OR 100mg acalabrutinib twice
a day OR 160mg zanubrutinib twice a day OR 320mg zanubrutinib each day.
Study burden and risks
Subject*s participation in this study will last 44 months and consists of a
screening period, treatment period and a follow-up period. During the treatment
period, subjects will need to visit the study site after 2 and 4 weeks during
the first cycle and every 4 weeks during the next cycles. During the follow-up
period, subjects will be contacted every 6 months for survival. Aside from the
intervention described above, participation in this study involves blood draws
at multiple visits, biopsy at screening and might involve radiation exposure
through CT, PET/CT or MRI scans. Participants will be subjected to: blood
draws, tumor tissue biopsy, bone marrow biopsy, GI biopsy, questions regarding
medical history, use of concomitant medications/procedures, general well-being
and adverse events; urine sampling; measurement of vital signs; physical and
neurological examination; performance status assessment; measurement of weight;
ECGs, patient reported outcomes questionnaires.
Subjects will be expected to take the drug in the way the investigator
explained, not have had any other investigational drugs within 2 weeks before
start taking study drug or while taking study drug, not have had major surgery
within 4 weeks before start taking study drug, not take vaccination with live
vaccines within 28 days of dosing, during the study and within 90 days after
the last dose of study treatment, keep their appointments for visits, honestly
answer all study questions, keep a patient card with them at all times, avoids
foods that are inhibitors of CYP3A4 and drugs that are inhibitors of
p-glycoprotein, not get pregnant or make someone pregnant during the study and
for 6 months after the last dose of study drug.
The following side effects have been observed in greater than or equal to 5% of
patients receiving LOXO-305: Abdominal pain; Back pain; Bruising; Constipation;
Cough; Decreased hemoglobin in your blood (anemia) which can cause tiredness
and shortness of breath; Decreased white blood cells in your blood which may
increase your risk of infection; Diarrhea; Dizziness; Fatigue (tiredness);
Fever; Headache; Increase in a blood salt called uric acid which is usually due
to cancer cells dying. Untreated high uric acid levels can lead to kidney
damage; Nausea; Red bumpy rash; Shortness of breath; Swelling of legs or hands;
Upper respiratory infection.
The following side effects have been mainly observed in patients receiving
treatment with approved BTK inhibitor ibrutinib (I): abnormal bleeding (I);
infections (I) including serious and fatal events; low blood counts, including
low neutrophils (which fight infection and low platelets (which help blood to
clot) (I); abnormal heart rhythms (I); high blood pressure (I); secondary
cancers (I); complications affecting kidney function or blood salt levels when
cells rapidly die (I); harmful effects on an embryo or fetus (I); rash;
musculoskeletal pain; low potassium. The study drugs may cause unforeseeable
risks to pregnant women or to unborn babies.
LOXO-305 has demonstrated clinical activity in the patient population specified
for this study. LOXO-BTK-18001 (NCT03740529) is a first in human global Phase
1/ 2 study evaluating the safety and efficacy of LOXO-305 in patients with CLL
and B-cell NHL who have failed or are intolerant to standard of care therapy.
Efficacy data from the LOXO-BTK-18001 study show robust and durable anti-tumor
activity against a variety of B-cell malignancies including covalent BTK
inhibitor pretreated MCL. The safety profile in Study LOXO-BTK-18001 is
reflective of the selectivity of LOXO-305. Additional information about the
known and expected risks, serious adverse events (SAEs), and reasonably
anticipated AEs of LOXO-305, is provided in the Investigator*s Brochure
(LOXO-305 IB). When viewed as a whole, the benefit/risk ratio is favorable for
LOXO-305 as monotherapy in the proposed patient population to be evaluated in
this study.
Tresser Boulevard 281
Stamford CT 06901
US
Tresser Boulevard 281
Stamford CT 06901
US
Listed location countries
Age
Inclusion criteria
• At least 18 years of age
• Confirmed diagnosis by local laboratory of MCL with documentation of
overexpression of cyclin D1 with at least one B-cell marker (e.g., CD19,
CD20, or PAX5) and/or t (11;14), by cytogenetics, fluorescent in situ
hybridization (FISH) or polymerase chain reaction.
• Previously treated with at least one prior line of systemic therapy for
MCL.
•Measurable disease by PET-CT and/or CT/MRI as defined by Lugano
criteria and aligned with protocol imaging requirements:
- PET-CT: FDG (fluorodeoxyglucose) avid lymphoma lesion
- at least one nodal lesion (> 1.5 cm in long axis) or extranodal
lesion (> 1.0 cm in long axis) measurable in 2 dimensions, not
previously radiated (unless progression has been radiographically
documented following radiation therapy).
• Documented evidence of radiographically and/or histologically
confirmed PD on the most recent line of therapy or relapse prior to study
enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate organ function
• Must have life expectancy of at least 3 months
Exclusion criteria
• Current suspected or confirmed active CNS involvement with MCL or
previous CNS involvement.
• Prior treatment with an approved or investigational BTK inhibitor.
• Major surgery within 4 weeks prior to randomization.
• History of bleeding diathesis.
• History of stroke or intracranial hemorrhage within 6 months of
randomization.
• History of allogeneic or autologous stem cell transplant (SCT) or
chimeric antigen receptor-modified T-cell (CAR-T) therapy within 60
days of randomization.
• Significant cardiovascular disease.
• Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec
during Screening.
• Known human immunodeficiency virus (HIV) infection, regardless of
CD4 count.
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection.
• Known active cytomegalovirus (CMV) infection. Unknown or negative
status are eligible.
• Pregnancy during the study or within 3 months of the last dose of study
treatment.
• Clinically significant active malabsorption syndrome or other condition
likely to affect gastrointestinal (GI) absorption of the study drug.
• Evidence of other clinically significant uncontrolled condition(s)
including but not limited to, uncontrolled systemic bacterial, viral, fungal
or parasitic infection (except for fungal nail infection), or other clinically
significant active disease process which in the opinion of the investigator
and medical monitor may pose a risk for patient participation. Screening
for chronic conditions is not required.
•History of second malignancy unless in remission for at least 2 years; in-situ
carcinomas not requiring treatment intervention, , non-melanoma skin cancer
curatively treated, nonmetastatic breast, or nonmetastatic prostate cancer
where hormonal therapy is being continued as standard of care are allowed.
Prior/Concomitant Therapy
• Ongoing chronic treatment with strong cytochrome P450 3A4
(CYP3A4) inhibitors or inducers which cannot be stopped within 3-5
half-lives of the CYP3A inhibitor therapy prior to start of study drug
treatment.
Because of their effect on CYP3A4, use of any of the following within 3
days of study therapy start is prohibited: Grapefruit or grapefruit
products, Seville oranges or products from Seville oranges, Star fruit or
star fruit products.
• Steroid use with antineoplastic intent within 7 days of study drug
initiation.
• Patients requiring therapeutic anticoagulation with warfarin or another
vitamin K antagonist.
• Vaccination with a live vaccine within 28 days prior to randomization.
• Have a known hypersensitivity to any of the excipients of pirtobrutinib
or to the intended covalent BTK inhibitor if randomized to control arm.
•Laction, or plan to breastfeed during the study or within 2 weeks of the last
dose of study treatment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-507695-52-00 |
| EudraCT | EUCTR2020-004553-72-NL |
| ClinicalTrials.gov | NCT04662255 |
| CCMO | NL76907.056.21 |