A Phase 3 Study Comparing LOXO-305 to Investigator’s Choice of Idelalisib plus Rituximab or Bendamustine plus Rituximab
- Conditions
- Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaMedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004554-30-CZ
- Lead Sponsor
- oxo Oncology Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
1.Age 18 or older per local regulations at time of enrollment.
2.Confirmed diagnosis by redacted local laboratory report of CLL/SLL
as defined by iwCLL 2018 criteria, including the following:
a)B-cells coexpressing the surface antigen CD5 together with at least
one B-cell antigen(CD19, CD20, CD23) and either ? or?? light-chain
restricted.
b) = 5 × 109 B lymphocytes/L (5000/µL) in the peripheral blood. For
SLL patients, history of = 5 × 109 B lymphocytes/L (5000/µL) in the
peripheral blood is allowed.
c)Prolymphocytes may comprise = 55% of blood lymphocytes.
3.A requirement for therapy consistent with iwCLL 2018 criteria for
initiation of therapy such that at least 1 of the following should be met:
a)Evidence of progressive marrow failure as manifested by the
development of, or worsening of, anemia (such as hemoglobin < 10
g/dL) and/or thrombocytopenia(such as platelets = 100 × 109/L).
b)Massive (i.e., spleen edge = 6 cm below the left costal margin) or
progressive or symptomatic splenomegaly(= 13 cm).
c)Massive nodes (i.e., = 10 cm in longest diameter) or progressive or
symptomatic lymphadenopathy.
d)Progressive lymphocytosis with an increase of > 50% over a 2-
month period or lymphocyte doubling time < 6 months. Factors
contributing to lymphocytosis other than CLL/SLL (e.g., infections,
steroid administration)should be excluded.
e)Autoimmune complications including anemia or thrombocytopenia
poorly responsive to corticosteroids.
f)Symptomatic or functional extranodal involvement(e.g., skin,
kidney, lung, spine).
g)Disease-related symptoms (also known as B-symptoms) as defined
by any of the following:
i)Unintentional weight loss = 10% within the previous 6 months.
ii)Significant fatigue(i.e., Eastern Cooperative Oncology Group [ECOG]
performance scale 2 or worse; cannot work or unable to perform usual
activities).
iii)Fevers = 100.5°F or 38.0°C for 2 or more weeks without evidence of
infection.
iv)Night sweats for = 1 month without evidence of infection.
4.Known 17p deletion status(wildtype for 17p locus or positive for 17p
deletion)by FISH see Section 1.2.2.
5.Previously treated with a covalent BTK inhibitor, investigational or
approved, and either alone or in combination with other agents. Patients
may have received an unlimited number of lines of prior therapy.
6.Eastern Cooperative Oncology Group(ECOG)0-2.
7.Must have adequate organ function, as defined below. These values
must be met during the Screening Period. Results from the most recent
assessment will be used for eligibility.
8.Patients are required to have had the following washout periods
prior to planned C1D1:
a)Targeted agents or cytotoxic chemotherapy: 5 half-lives or 2 weeks,
whichever is shorter
b)Anticancer therapeutic monoclonal antibodies: 4 weeks; patients
who crossover are not required to observe this washout period
c)Palliative limited field radiation: 7 days
d)Broad field radiation(= 30% of bone marrow or whole brain
radiotherapy): 28 days
9.Prior treatment related AEs must have recovered to Grade =?1,
pretreatment baseline, or are controlled with medications without
meeting other exclusion criteria (with the exception of alopecia).
10.Willingness of men and women of childbearing potential(WOCBP),
and their partners, to observe barrier and/or highly effective birth
control methods as outlined in Section 10.2(Appendix 2) for the
duration of treatment and for 6 months following the last dose of study
treatment or 12 months after the last dose of rituximab, whichev
1. Known or suspected Richter's transformation to diffuse large B-cell
lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at
any time preceding enrollment.
2. Known or suspected history of central nervous system (CNS)
involvement by CLL/SLL.
3. Patients who experienced a major bleeding event on a prior BTK
inhibitor. Refer to Protocol for definition of major bleeding.
4. Active second malignancy; patients with treated second malignancy
who are in remission with life expectancy > 2 years and with
documented Sponsor approval are eligible.
5. Major surgery, within 4 weeks of planned start of study treatment.
6. History of or ongoing drug-induced pneumonitis.
7. Ongoing drug-induced liver injury, primary biliary cirrhosis and/or
extrahepatic obstruction caused by cholelithiasis and cirrhosis of the
liver.
8. History of allogeneic or autologous SCT or CAR-T therapy within the
past 60 days.
9. Active uncontrolled auto-immune cytopenia (e.g., autoimmune
hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
not on a stable regimen and dose for at least 4 weeks prior to study
enrollment.
10. Significant cardiovascular disease. For definitions see Protocol.
11. Prolongation of the QT interval corrected (QTc) for heart rate using
Fridericia's Formula (QTcF) > 470 msec on at least 2 of 3 consecutive
electrocardiograms (ECGs), and mean QTcF > 470 msec on all 3 ECGs,
during Screening.
a) QTcF is calculated using Fridericia's Formula (QTcF = QT/(RR^0.33)
b) Correction of suspected drug-induced QTcF prolongation or
prolongation due to electrolyte abnormalities can be attempted at the
Investigator's discretion, and only if clinically safe to do so with either
discontinuation of the offending drug or switch to another drug not
known to be associated with QTcF prolongation or electrolyte
supplementation.
c) Correction of QTc for underlying bundle branch block (BBB)
permissible.
12. Hepatitis B or hepatitis C testing indicating active/ongoing infection.
Refer to Protocol for screening laboratory tests.
13. Known active cytomegalovirus (CMV) infection. Patients with
negative status are eligible.
14. Evidence of other clinically significant uncontrolled condition(s)
including, but not limited to, uncontrolled systemic infection (viral,
bacterial, or fungal) 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.
15. Known Human Immunodeficiency Virus (HIV) infection, regardless of
CD4 count. Patients with unknown or negative status are eligible.
16. Clinically significant active malabsorption syndrome or other
condition likely to affect gastrointestinal (GI) absorption of the oraladministered
study treatments.
17. Ongoing inflammatory bowel disease.
18. Prior exposure to non-covalent (reversible) BTK inhibitor.
19. Concurrent use of investigational agent or anticancer therapy except
hormonal therapy.
20. Patients requiring therapeutic anticoagulation with warfarin or
another Vitamin K antagonist.
21. Use of > 20 mg prednisone QD or equivalent dose of steroid per day
at the time of C1D1. Patients may not be on prednisone of any dose
intended for antineoplastic use.
22. For patients planned to receive idelalisib: Current treatment with
strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers
(refer to Section 10.4). Because of their effect on CYP3A4, use of any of
the foll
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) compared to investigator’s choice of idelalisib plus rituximab<br>(IdelaR) or bendamustine plus rituximab (BR) (Arm B).;Secondary Objective: •To evaluate the effectiveness of Arm A compared to Arm B based on overall response rate (ORR) and time to event(s) outcomes<br>•To evaluate the safety and tolerability of each treatment arm<br>•To evaluate the effectiveness of Arm A compared to Arm B based on patient reported outcomes;Primary end point(s): Assessed by Independent Review Committee (IRC):<br>• PFS per iwCLL 2018;Timepoint(s) of evaluation of this end point: The time from the date of randomization until PD or death from any cause, whichever occurs first
- Secondary Outcome Measures
Name Time Method