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 (CLLRT2)
The aim of the trial is to Evaluate the Efficacy of Pirtobrutinib and Epcoritamab Compared With R-(Mini)-CHOP for Treatment of Patients With DLBCL-type Richter Transformation
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
This trial is a phase 2 study and - according to the definitions of the ICH Harmonized Tripartite Guide-line E8 - a therapeutic exploratory type of study, which is designed as a prospective, multicenter, open label trial. The trial aims to investigate the efficacy and safety of a fixed-duration treatment ap-proach in patients aged 80 years or older and/or those exhibiting symptoms of frailty.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 2 단계
연락처 및 위치
연구 장소
-
-
-
Copenhagen, 덴마크, 2100
- 아직 모집하지 않음
- Rigshospitalet
-
연락하다:
- Caspar Da Cunha-Bang, MD
- 전화번호: +4535450410
- 이메일: Caspar.Da.Cunha-Bang@regionh.dk
-
-
-
-
-
Cologne, 독일, 50937
- 모병
- Uniklinik Köln
-
연락하다:
- Barbara Eichhorst, Prof.
- 전화번호: +4922147888220
- 이메일: barbara.eichhorst@uk-koeln.de
-
Dresden, 독일, 01307
- 아직 모집하지 않음
- Technische Universitaet Dresden
-
연락하다:
- Johannes Schetelig, Prof.
- 전화번호: +493514585604
- 이메일: Johannes.Schetelig@ukdd.de
-
Frankfurt, 독일, 60590
- 모병
- Universitätsklinikum Frankfurt
-
연락하다:
- Sebastian Scheich
- 전화번호: +496963013767
- 이메일: s.scheich@med.uni-frankfurt.de
-
Heidelberg, 독일, 69120
- 아직 모집하지 않음
- Universitätsklinikum Heidelberg
-
연락하다:
- Peter Dreger, Prof.
- 전화번호: +496221568030
- 이메일: Peter.Dreger@med.uni-heidelberg.de
-
Kiel, 독일, 24105
- 아직 모집하지 않음
- Universitätsklinikum Schleswig-Holstein Campus Kiel
-
연락하다:
- Matthias Ritgen, Dr.
- 전화번호: +4943150022555
- 이메일: m.ritgen@med2.uni-kiel.de
-
Ulm, 독일, 89081
- 모병
- Universitätsklinik Ulm
-
연락하다:
- Christof Schneider, Dr.
- 전화번호: +4973150056012
- 이메일: christof.schneider@uniklinik-ulm.de
-
-
-
-
-
Dublin, 아일랜드, Dublin 9
- 모병
- Beaumont Hospital
-
연락하다:
- Patrick Thornton
- 전화번호: +613 8559 5000
- 이메일: philip.thompson@petermac.org
-
Galway, 아일랜드, H91 YR71
- 모병
- University Hospital Galway
-
연락하다:
- Amjad Hayat
- 전화번호: +35391544281
- 이메일: amjad.hayat@hse.ie
-
-
-
-
-
Innsbruck, 오스트리아, 6020
- 아직 모집하지 않음
- Medizinische Universitaet Innsbruck
-
연락하다:
- Dominik Wolf, Prof.
- 전화번호: +4351250424003
- 이메일: mui-oversight@i-med.ac.at
-
Vienna, 오스트리아, 1090
- 모병
- Medizinische Universität Wien
-
연락하다:
- Alexander Gaiger
- 전화번호: +4314040044765
- 이메일: alexander.gaiger@meduniwien.ac.at
-
-
-
-
-
Melbourne, 호주, 3000
- 모병
- Peter MacCallum Cancer Center
-
연락하다:
- Philip Thompson, Prof.
- 전화번호: +613 8559 5000
- 이메일: philip.thompson@petermac.org
-
-
참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
-
Age ≥80 years OR considered frail defined by a frailty score of >2 on the FRAIL scale via the patient´s assessment
-
Has documented treatment-naïve CLL or small lymphocytic lymphoma (SLL) according to iwCLL 2018 criteria3
-
CLL/SLL requiring treatment according to the iwCLL 2018 criteria3
-
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)
-
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
-
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).
-
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
-
Life expectancy ≥ 3 months
-
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
-
Signed informed consent and, in the investigator's judgment, able to comply with the study protocol
-
Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
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
-
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
활성 비교기: 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 |
750 mg/m2 iv (R-CHOP) or 400 mg/m2 iv (R-mini-CHOP) 50 mg/m2 iv (R-CHOP) or 25 mg/m2 iv (R-mini-CHOP) 1.4 mg/m2 iv (R-CHOP) or 1 mg/m2 iv (R-mini-CHOP) 375 mg/m2 iv (R-CHOP) or 375 mg/m2 iv or sc (R-mini-CHOP) |
|
실험적: 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. |
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
다른 이름들:
Pirtobrutinib 200 mg QD po
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
PFS
기간: approx. 40 months after first subject in
|
Investigator-assessed progression-free survival (PFS) according to Lugano criteria |
approx. 40 months after first subject in
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
ORR
기간: approx. 40 months after first subject in
|
Overall response rate (ORR) at the end of (combination) treatment according to Lugano criteria |
approx. 40 months after first subject in
|
|
CRR
기간: approx. 40 months after first subject in
|
Complete response rate (CRR) at the end of (combination) treatment according to Lugano criteria |
approx. 40 months after first subject in
|
|
Best response according to Lugano criteria
기간: approx. 40 months after first subject in
|
Best response according to Lugano criteria |
approx. 40 months after first subject in
|
|
Undetectable minimal residual disease (uMRD)
기간: approx. 40 months after first subject in
|
Undetectable minimal residual disease (uMRD) rates in peripheral blood at the end of (combination) treatment |
approx. 40 months after first subject in
|
|
DOR
기간: approx. 40 months after first subject in
|
Duration of response (DOR) according to Lugano criteria |
approx. 40 months after first subject in
|
|
Overall survival (OS)
기간: approx. 40 months after first subject in
|
Overall survival (OS) |
approx. 40 months after first subject in
|
|
TTNT
기간: approx. 40 months after first subject in
|
Time to next treatment (TTNT) |
approx. 40 months after first subject in
|
|
TFS
기간: approx. 40 months after first subject in
|
Treatment-free survival (TFS) |
approx. 40 months after first subject in
|
|
SCT
기간: approx. 40 months after first subject in
|
Proportion of patients receiving allogeneic stem cell transplantation (SCT) for consolidation |
approx. 40 months after first subject in
|
공동 작업자 및 조사자
협력자
협력자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 아미노산, 펩티드 및 단백질
- 단백질
- 유기 화학 물질
- 이종 사이 클릭 화합물
- 이종 사이 클릭 화합물, 2- 링
- 이종 사이 클릭 화합물, 융합 링
- 탄화수소
- 탄화수소, 순환
- 탄수화물
- 알칼로이드
- 다 환식 방향족 탄화수소
- 탄화수소, 방향족
- 다 환식 화합물
- 글리코 사이드
- 인돌
- 항체, 모노클로 날
- 항체
- 면역 글로불린
- 면역 단백질
- 혈액 단백질
- 혈청 글로불린
- 글로불린
- 포스 포 아미드 머스타드
- 질소 머스타드 화합물
- 겨자 화합물
- 탄화수소, 할로겐화
- 포스 포 아미드
- 유기 인 화합물
- Vinca 알칼로이드
- Secologanin Tryptamine 알칼로이드
- 인돌 알칼로이드
- 인돌리 지딘
- 인도인
- 안트라 사이클린
- 나프 타센
- 아미노 글리코 시드
- 항체, 모노클로 날, 뮤린 유래
- Daunorubicin
- 리툭시맙
- 시클로포스파미드
- 독소루비신
- 빈크리스틴
- Pirtobrutinib
기타 연구 ID 번호
기타 연구 ID 번호
- CLLRT2
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .