Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07917780




Registration number
Help: Registration number
NCT07917780
Ethics application status
Help: Ethics application status
Date submitted
Help: Date submitted
28/10/2026
Date registered
Help: Date registered
5/11/2026
Date last updated
Help: Date last updated
5/11/2026

Titles & IDs
Public title
A Prospective, Open-label, Randomized, Multicenter Phase-III Trial to Evaluate the Efficacy of Pirtobrutinib and Epcoritamab Compared With R-(Mini)-CHOP for Treatment of Patients With DLBCL-type Richter Transformation
Scientific title
A Prospective, Open-label, Randomized, Multicenter Phase-III Trial to Evaluate the Efficacy of Pirtobrutinib and Epcoritamab Compared With R-(Mini)-CHOP for Treatment of Patients With DLBCL-type Richter Transformation
Additional trial identifiers [1] 0 0
CLLRT2
Universal Trial Number (UTN)
Trial acronym
CLLRT2
Related trial records

Health condition
Health condition(s) studied:
Richter Transformation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Treatment: Other - Epcoritamab
Treatment: Drugs - Pirtobrutinib
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Rituximab

Active comparator: Arm A: R-(mini)-CHOP - Cycle 1-6 Day 1: Cyclophosphamide 750 mg/m2 iv Doxorubicin 50 mg/m2 iv Vincristine 1.4 mg/m2 (max 2 mg) iv Rituximab 375 mg/m2 iv Day 1-5: Prednisolone 100 mg po

If R-CHOP-ineligible\*, R-mini-CHOP3 is administered:

Cycle 1-6 Day 1: Cyclophosphamide 400 mg/m2 iv Doxorubicin 25 mg/m2 iv Vincristine 1 mg iv Rituximab 375 mg/m2 iv or sc Day 1-5: Prednisolone 100 mg po

Experimental: Arm B: Epcoritamab-Pirtobrutinib - 12 cycles: Cycle 1 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 0.16 mg sc Day 8: Epcoritamab 0.8 mg sc Day 15: Epcoritamab 48 mg sc

Cycle 2-4 Day 1-21: Pirtobrutinib 200 mg QD po Day 1, 8, 15: Epcoritamab 48 mg sc

Cycle 5+6 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 48 mg sc

Cycle 7-12:

Day 1-28: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 48 mg sc

For patients with CR, PR or SD after 12 cycles (=EO\[C\]T), maintenance treatment with pirtobrutinib 200 mg QD until unacceptable toxicity, disease progression or allogeneic stem cell transplantation will be offered.


Treatment: Other: Epcoritamab
Cycle 1 Day 1-21: Pirtobrutinib 200 mg QD po Day 1: Epcoritamab 0.16 mg sc Day 8: Epcoritamab 0.8 mg sc Day 15: Epcoritamab 48 mg sc

Cycle 2-28 Epcoritamab 48 mg sc

Treatment: Drugs: Pirtobrutinib
Pirtobrutinib 200 mg QD po

Treatment: Drugs: Cyclophosphamide
750 mg/m2 iv (R-CHOP) or 400 mg/m2 iv (R-mini-CHOP)

Treatment: Drugs: Doxorubicin
50 mg/m2 iv (R-CHOP) or 25 mg/m2 iv (R-mini-CHOP)

Treatment: Drugs: Vincristine
1.4 mg/m2 iv (R-CHOP) or 1 mg/m2 iv (R-mini-CHOP)

Treatment: Drugs: Rituximab
375 mg/m2 iv (R-CHOP) or 375 mg/m2 iv or sc (R-mini-CHOP)
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Description of the comparator or control
Control group

Outcomes
Primary outcome [1] 0 0
PFS
Timepoint [1] 0 0
approx. 40 months after first subject in
Secondary outcome [1] 0 0
ORR
Timepoint [1] 0 0
approx. 40 months after first subject in
Secondary outcome [2] 0 0
CRR
Timepoint [2] 0 0
approx. 40 months after first subject in
Secondary outcome [3] 0 0
Best response according to Lugano criteria
Timepoint [3] 0 0
approx. 40 months after first subject in
Secondary outcome [4] 0 0
Undetectable minimal residual disease (uMRD)
Timepoint [4] 0 0
approx. 40 months after first subject in
Secondary outcome [5] 0 0
DOR
Timepoint [5] 0 0
approx. 40 months after first subject in
Secondary outcome [6] 0 0
Overall survival (OS)
Timepoint [6] 0 0
approx. 40 months after first subject in
Secondary outcome [7] 0 0
TTNT
Timepoint [7] 0 0
approx. 40 months after first subject in
Secondary outcome [8] 0 0
TFS
Timepoint [8] 0 0
approx. 40 months after first subject in
Secondary outcome [9] 0 0
SCT
Timepoint [9] 0 0
approx. 40 months after first subject in

Eligibility
Key inclusion criteria
1. Age =80 years OR considered frail defined by a frailty score of >2 on the FRAIL scale via the patient´s assessment
2. Has documented treatment-naïve CLL or small lymphocytic lymphoma (SLL) according to iwCLL 2018 criteria3
3. CLL/SLL requiring treatment according to the iwCLL 2018 criteria3
4. Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as follows, unless cytopenia is due to marrow involvement of CLL:

* Absolute neutrophil count = 1.0 × 10^9/L
* Platelet counts = 30 × 10^9/L; in cases of thrombocytopenia clearly due to marrow in-volvement of CLL (per the discretion of the investigator); platelet count should be = 10 × 10^9/L if there is bone marrow involvement
* Total haemoglobin = 9 g/dL (without transfusion support, unless anaemia is due to mar-row involvement of CLL)
5. Adequate liver function as indicated by a total bilirubin, AST, and ALT =2 times the institutional upper limit of normal (ULN) value unless directly attributable to the patient's CLL or Gilbert's syndrome
6. Adequate renal function defined by a value =30 mL/min, determined either by creatinine clearance directly measured with a 24-hour urine collection or via estimated GFR calculated according to the CKD-EPI equation or Cystatin C measurements (e.g. in sarcopenic patients).
7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed repeatedly until 6 months after last month of treatment), negative testing for hepa-titis C RNA within 6 weeks prior to registration
8. Life expectancy = 3 months
9. In case of a recent previous (i.e. debulking) treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods be-fore start of the study treatment in the CLL-Frail2 trial:

* chemotherapy = 28 days
* antibody treatment = 14 days
* corticosteroids may be applied until the start of the study therapy; these have to be re-duced to an equivalent of = 20mg prednisolone per day during treatment
10. Signed informed consent and, in the investigator's judgment, able to comply with the study protocol
11. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
* 1. Previous CLL-directed therapies 2. Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leu-kaemia) 3. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML) 4. Uncontrolled autoimmune condition 5. Malignancies other than CLL currently requiring systemic therapies (unless the malignant dis-ease is in a stable remission at the discretion of the treating physician) 6. Uncontrolled infection currently requiring systemic treatment 7. Any serious medical condition or abnormality in clinical laboratory tests that, in the investiga-tor's judgment, precludes the patient's safe participation in and completion of the study 8. Requirement of treatment with any moderate or strong CYP3A4 inhibitor or strong CYP3A4 inducer (= 14 days or 5 half-lives, whichever is shorter) before the first dose of study drug, or requiring ongoing treatment with a moderate or strong CYP3A inhibitor or a strong CYP3A in-ducer.

9. Requirement of therapy with phenprocoumon or other vitamin K antagonists 10. Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
* Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring for HBV reactivation
* Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable 11. Major surgery within 4 weeks of the first dose of study drug 12. Any uncontrolled or clinically significant cardiovascular disease including the following:
* New York Heart Association class III or IV congestive heart failure
* History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricu-lar fibrillation, torsades de pointes) 13. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand dis-ease if not CLL/SLL related, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 14. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery proce-dures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

15. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life [t1/2] of the compound, whichever is longer) prior to registration 16. Known hypersensitivity to zanubrutinib or sonrotoclax or any of the excipients 17. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment) 18. Fertile men or women of childbearing potential unless:
* surgically sterile or = 2 years after the onset of menopause, or
* willing to use two methods of reliable contraception including one highly effective contra-ceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 7 days after sonrotoclax and 30 days after zanubrutinib respec-tively 19. Vaccination with a live vaccine <28 days prior to registration 20. Legal incapacity 21. Prisoners or subjects who are institutionalized by regulatory or court order 22. Persons who are in dependence to the sponsor or an investigator

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/06/2026
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/05/2030
Actual
Sample size
Target
116
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Innsbruck
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Denmark
State/province [3] 0 0
Copenhagen
Country [4] 0 0
Germany
State/province [4] 0 0
Cologne
Country [5] 0 0
Germany
State/province [5] 0 0
Dresden
Country [6] 0 0
Germany
State/province [6] 0 0
Frankfurt
Country [7] 0 0
Germany
State/province [7] 0 0
Heidelberg
Country [8] 0 0
Germany
State/province [8] 0 0
Kiel
Country [9] 0 0
Germany
State/province [9] 0 0
Ulm
Country [10] 0 0
Ireland
State/province [10] 0 0
Dublin
Country [11] 0 0
Ireland
State/province [11] 0 0
Galway

Funding & Sponsors
Primary sponsor type
Other
Name
German CLL Study Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cancer Trials Ireland (CTI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Australasian Leukaemia & Lymphoma Group (ALLG)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Fondazione GIMEMA
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Nordic CLL Study Group (NCLLSG)
Address [4] 0 0
Country [4] 0 0

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


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/NCT07917780