소아 재발성 또는 불응성 백혈병, 림프종 또는 고형 종양 치료를 위한 포나티닙의 안전성 및 효능
소아 참가자의 재발성 또는 불응성 백혈병, 림프종 또는 고형 종양 치료를 위한 포나티닙의 안전성 및 효능을 평가하는 공개, 단일군, 1/2상 연구
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Incyte Corporation Call Center (ex-US)
- 전화번호: +800 00027423
- 이메일: globalmedinfo@incyte.com
연구 장소
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Utrecht, 네덜란드, 03584
- 모병
- Princess Maxima Center For Pediatric Oncology
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Ghent, 벨기에, 09000
- 모병
- Ghent University Hospital
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Stockholm, 스웨덴, 14141
- 모병
- Karolinska University Hospital Solna
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Barcelona, 스페인, 08035
- 모병
- Hospital General Universitario Vall D Hebron
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Barcelona, 스페인, 08035
- 모병
- Hospital Sant Joan de Deu de Manresa
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Madrid, 스페인, 28009
- 모병
- Hospital Infantil Unversitario Nino Jesus
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Valencia, 스페인, 46026
- 모병
- Hospital Universitari I Politecnic La Fe
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Glasgow, 영국, G514TF
- 모병
- Royal Hospital For Sick Children Yorkhill Glasgow
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Liverpool, 영국, L12 2AP
- 모병
- Alder Hey Childrens Nhs Foundation Trust
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Sutton, 영국, SM2 5PT
- 모병
- The Royal Marsden Nhs Foundation Trust - Sutton
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Bologna, 이탈리아, 40138
- 모병
- Aou Policlinico S. Orsola-Malpighi
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Brescia, 이탈리아, 25123
- 모병
- Asst Degli Spedali Civili Di Brescia
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Genova, 이탈리아, 16147
- 모병
- Ospedale Pediatrico G. Gaslini
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Milan, 이탈리아, 20133
- 모병
- Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
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Monza, 이탈리아, 20900
- 모병
- University of Milano Bicocca
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Naples, 이탈리아, 80123
- 모병
- Aorn Santobono Pausilipon
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Pavia, 이탈리아, 27100
- 모병
- Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
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Rome, 이탈리아, 00165
- 모병
- Ospedale Pediatrico Bambino Gesu Irccs
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Torino, 이탈리아, 10126
- 모병
- A.O.U Citta Della Salute E Della Scienza Di Torino Presidio Ospedaliero Infantile Regina Margherita
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Paris, 프랑스, 75019
- 모병
- Hopital Robert Debre
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Paris, 프랑스, 75571
- 모병
- Armand Trousseau Hospital
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Poitiers, 프랑스, 86021
- 모병
- Centre Hospitalier Universitaire de Poitiers
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Rennes, 프랑스, 35203
- 완전한
- Chu de Rennes - Hospital Sud
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of the following malignancies:
- Phase 1: CP-CML, BP-CML, AP-CML ALL. AML. Other leukemias. Lymphoma. Any other tumors, including tumors of the CNS, for which standard therapy is not available or is not indicated.
- Phase 2, Group A with CP-CML: CP-CML at the time of study entry and must be resistant to or intolerant of at least 1 prior BCR-ABL-targeted TKI therapy or be in "warning" response status or have the T315I kinase domain mutation.
Must have 1 bone marrow aspirate with documentation of BCR-ABL translocation by conventional cytogenetics, metaphase FISH, or q-PCR performed within 42 days before the first dose of ponatinib.
- Phase 2, Group B with other leukemias or solid tumors: ALL. AML. Other leukemias. Lymphoma. Any other tumors, including tumors of the CNS, with mutations of RET, FLT3, KIT, FGFR, PDGFR, TIE2, VEGFR, or any other mutations where ponatinib may have biological activity (eg, EPH receptors and SRC families of kinases) as assessed on fresh or archived tumor tissue.
Participants with solid tumors or with lymphoma must have measurable disease by CT or MRI based on RECIST v1.1 or the Lugano lymphoma guidelines as determined by site radiology.
Prior therapies as follows:
- Phase 1: Participants with CML who are resistant to or intolerant of (as defined Appendix F) to at least 1 prior BCR-ABL-targeted TKI therapy.
Participants with ALL who have progressed on or after all available or indicated therapies, which may have included 1 prior BCR-ABL-targeted TKI therapy.
Participants with AML or other leukemias who have progressed on or after at least 1 prior induction attempt (for France only) or for whom no effective standard therapy is available or indicated (other countries).
Participants with solid tumors (including tumors of the CNS) or lymphomas who have progressed despite standard therapy or for whom no effective standard therapy is available or indicated.
- Phase 2, Group A with CP-CML: Participants who are resistant to or intolerant of at least 1 prior BCR-ABL-targeted TKI therapy.
- Phase 2, Group B with other leukemias or solid tumors: Participants with ALL who have progressed on or after all available or indicated therapies, which must have included 1 prior BCR-ABL-targeted TKI therapy.
Participants with AML or other leukemias who have progressed on or after at least 1 prior induction attempt (for France only) or for whom no effective standard therapy is available or indicated (other countries).
Participants with solid tumors (including tumors of the CNS) or lymphomas who progressed despite standard therapy or for whom no effective standard therapy is available or indicated.
- Karnofsky performance status ≥ 40% for participants ≥ 16 years old or Lansky Play Scale ≥ 40% for pediatric participants < 16 years old.
- Participants must have recovered to < Grade 2 per the NCI CTCAE v5.0 or to baseline from any non-hematologic toxicities (except alopecia) due to previous therapy.
- Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
Prior therapies:
- Participants with BP-CML, ALL, or AML who have received any of the following: Corticosteroids or hydroxyurea within 24 hours before the first dose of ponatinib.
Vincristine within 7 days before the first dose of ponatinib. Other chemotherapy (excluding intrathecal chemotherapy) within 14 days before the first dose of ponatinib.
- Participants (except the BP-CML, ALL, and AML participants described above) who: Have had cytotoxic chemotherapy within 21 days (or 42 days for nitrosoureas or mitomycin C) before the first dose of ponatinib.
Prior radiation therapy or radio-isotope therapy within 6 weeks before the first dose of ponatinib except local radiotherapy for palliative indication within 14 days before the first dose of ponatinib.
Autologous or allogeneic stem cell transplant < 3 months before the first dose of ponatinib.
Major surgery within 14 days before the first dose of ponatinib. Inadequate recovery and/or complications from a major surgery before starting therapy.
Prior treatment with any of the following:
- Immunosuppressive therapy (including post stem cell transplant regimens) within 14 days before the first dose of ponatinib.
- Any targeted cancer therapy (including TKIs) within 7 days before the first dose of ponatinib.
- Any other investigational anticancer agents within 30 days or 5 half-lives, whichever is longer, before randomization.
- Any monoclonal antibody-directed anticancer therapy within 5 half-lives of the first dose of ponatinib.
- Any chimeric antigen receptor therapy within 28 days before the first dose of ponatinib
- Ponatinib
- Protocol-defined lab Values
- Significant concurrent, uncontrolled medical condition, including but not limited to the following:
- Pancreatic: clinical, radiological, or laboratory evidence of pancreatitis.
- Cardiac:
- SF < 27% by ECHO, OR EF < 50% by MUGA.
- Abnormal QTcF on screening ECG, defined as QTcF of ≥ 450 ms.
- Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute MI within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV CHF (see Appendix P), and arrhythmia requiring therapy unless approved by the medical monitor/sponsor.
- Uncontrolled hypertension.
- Currently taking drug(s) that are known to have a risk of causing prolonged QTc or TdP unless the drug(s) can be changed to acceptable alternatives (ie, an alternate class of agents that do not affect the cardiac conduction system), or the participant can safely discontinue the drug(s).
- Cerebral:
- Participants with solid tumors with intracranial metastasis OR participants with active CNS leukemia (ie, CNS-2 status [< 5/μL WBCs and cytospin positive for blasts, or ≥ 5 /μL WBCs but negative by Steinherz/Bleyer algorithm (equation used for traumatic lumbar punctures), disseminated leptomeningeal disease, or CNS chloroma.
- Pre-existing significant CNS pathology including history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement.
- History of cerebrovascular ischemia/hemorrhage with residual deficits.
- Note: Participants with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved clinically according to Inclusion Criterion 6.
- Uncontrolled seizure disorder.
- Coagulation:
- Significant bleeding disorder or thrombophilia unrelated to the underlying malignancy indication for study participation.
- Gastrointestinal:
- Gastrointestinal disorders, such as malabsorption syndrome or any other illness that could affect oral absorption.
- Genetic:
- Participants with DNA fragility syndromes, such as Fanconi anemia and Bloom syndrome.
- Participants with Down syndrome.
- Participants with any active ≥ Grade 2 graft versus host disease.
- Chronic or current active uncontrolled infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
- Active HBV or HCV infection that requires treatment or at risk for HBV reactivation. Hepatitis B virus DNA and HCV RNA must be undetectable upon testing. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive.
- Known HIV infection.
- Current use of prohibited medication (see Section 6.7.2).
- Known hypersensitivity or severe reaction to ponatinib or excipients of ponatinib.
- Receipt of live (including attenuated) vaccines or anticipation of need for such vaccines during the study.
- Inability or unlikeliness to comply with the dose schedule and study evaluations, in the opinion of the investigator.
- Females who are pregnant or lactating.
- Other exclusions may apply.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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실험적: Ponatinib
Phase 1: Ponatinib administered according to age-based cohort doses and formulations to determine the maximum tolerated dose and recommended Phase 2 dose. Phase 2: Ponatinib administered at the recommended Phase 2 dose. |
Ponatinib administered as a tablet or age-appropriate formulation for pediatric participants according to age-based cohort assignment.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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2상: 포나티닙의 효능을 결정하기 위해 BCR-ABL 양성 백혈병 이외의 백혈병 환자를 대상으로 완전 반응(CR)으로 평가한 포나티닙의 효능
기간: 6 개월
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6 개월
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Phase 1: Number of dose-limiting toxicities
기간: 28 days
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Defined as the occurrence of any protocol-defined toxicities occurring after dosing and up to and including Day 28, except those toxicities with a clear alternative explanation. |
28 days
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Phase 2: Efficacy of ponatinib assessed by major cytogenetic response (MCyR) in participants with chronic-phase chronic myeloid leukemia (CP-CML)
기간: 12 months
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Defined as complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) as assessed by conventional cytogenetics or fluorescence in situ hybridization (FISH). |
12 months
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Phase 2: Efficacy of ponatinib assessed by major hematologic response (MaHR) or major molecular response (MMR) in participants with BCR-ABL-positive leukemias
기간: 3 months
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Assessed by polymerase chain reaction (PCR). |
3 months
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Phase 2: Efficacy of ponatinib assessed by incomplete complete response (iCR) in participants with leukemias other than BCR-ABL-positive leukemias
기간: 6 months
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Assessed by conventional cytogenetics, FISH, or PCR. |
6 months
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Phase 2: Efficacy of ponatinib assessed by CR in participants with lymphoma
기간: 6 months
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According to Lugano criteria based on computed tomography (CT) or magnetic resonance imaging (MRI) (or positron emission tomography [PET]). |
6 months
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Phase 2: Efficacy of ponatinib assessed by overall response rate in participants with solid tumors
기간: 6 months
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Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for central nervous system (CNS) tumors or Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for other solid tumors based on CT or MRI (or PET). |
6 months
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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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1상: 치료 관련 이상 반응의 수
기간: 6 개월
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6 개월
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1상 및 2상: CP-CML 참가자의 완전 혈액학적 반응(CHR)
기간: 6 개월
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6 개월
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1단계 및 2단계: CP-CML 참가자의 CCyR
기간: 12 개월
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12 개월
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1단계 및 2단계: CP-CML 참가자의 MMR
기간: 12 개월
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12 개월
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1단계: BCR-ABL 양성 백혈병 또는 CP-CML 이외의 백혈병 환자의 CR.
기간: 6 개월
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6 개월
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2상: BCR-ABL 양성 백혈병(AP-CML, BP-CML 또는 Ph+ALL) 참가자를 대상으로 MaHR 또는 MMR로 평가한 포나티닙의 항암 활성
기간: 3 개월
|
3 개월
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2상: BCR-ABL 양성 백혈병 이외의 백혈병 환자에서 CR로 평가한 포나티닙의 항암 활성
기간: 6 개월
|
6 개월
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2상: 치료 관련 이상 반응의 수
기간: 6 개월
|
6 개월
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2단계: 포나티닙의 소아과 친화적 제형 허가
기간: 6 개월
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6 개월
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2단계: 포나티닙 소아친화제제의 분포량
기간: 6 개월
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6 개월
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2상: 포나티닙 소아 친화적 제형의 AUC
기간: 6 개월
|
6 개월
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Phase 1: Tmax of ponatinib
기간: 6 months
|
Time to maximum concentration. |
6 months
|
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Phase 1: AUCss,0-24 of ponatinib
기간: 6 months
|
Area under the steady-state plasma or serum concentration-time curve from Hour 0 to 24. |
6 months
|
|
Phase 1: t½ of ponatinib
기간: 6 months
|
Apparent terminal-phase disposition half-life. |
6 months
|
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Phase 1: CLss/F of ponatinib
기간: 6 months
|
Apparent oral dose clearance at steady state. |
6 months
|
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Phase 1: Vz/F of ponatinib
기간: 6 months
|
Apparent oral dose volume of distribution. |
6 months
|
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Phase 1: MCyR in participants with BCR-ABL-positive leukemias
기간: 3 months
|
Defined as CCyR or PCyR as assessed by conventional cytogenetics or FISH. |
3 months
|
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Phase 1: MMR in participants with BCR-ABL-positive leukemias
기간: 3 months
|
Assessed by quantitative PCR (q-PCR). |
3 months
|
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Phase 1 and Phase 2: Time to response (TTR) in participants with CP-CML
기간: 6 months
|
Defined as the interval from the date of the first dose of study treatment to first response. |
6 months
|
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Phase 1 and Phase 2: Duration of response (DOR) in participants with CP-CML
기간: 6 months
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Defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met. |
6 months
|
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Phase 1 and Phase 2: Progression-free survival (PFS) in participants with CP-CML
기간: 6 months
|
Defined as the interval from the date of the first dose of study treatment until the date of progression of disease or the date of death from any cause, whichever is earlier. |
6 months
|
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Phase 1 and Phase 2: Overall survival (OS) in participants with CP-CML
기간: 6 months
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Defined as the interval from the date of the first dose of study treatment until death from any cause. |
6 months
|
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Phase 1: CRi in participants with leukemias other than BCR-ABL-positive leukemia or CP-CML
기간: 6 months
|
Assessed by conventional cytogenetics, FISH, or q-PCR. |
6 months
|
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Phase 1: CR in participants with lymphoma
기간: 6 months
|
According to Lugano criteria based on CT or MRI (or PET). |
6 months
|
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Phase 1: Overall response rate in participants with solid tumors
기간: 6 months
|
Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for CNS tumors or RECIST v1.1 for other solid tumors based on CT or MRI (or PET). |
6 months
|
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Phase 2: Anticancer activity of ponatinib assessed by CRi in participants with leukemias other than BCR-ABL-positive leukemias.
기간: 6 months
|
Assessed by conventional cytogenetics, FISH, or PCR. |
6 months
|
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Phase 2: Anticancer activity of ponatinib assessed by CR in participants with lymphoma
기간: 6 months
|
According to Lugano criteria based on CT or MRI (or PET). |
6 months
|
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Phase 2: Anticancer activity of ponatinib assessed by overall response rate in participants with solid tumors
기간: 6 months
|
Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for CNS tumors or RECIST v1.1 for other solid tumors based on CT or MRI (or PET). |
6 months
|
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Phase 2: OS in participants with solid tumors
기간: 6 months
|
Defined as the interval from the date of the first dose of study treatment until death from any cause. |
6 months
|
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Phase 2: DOR in participants with solid tumors
기간: 6 months
|
Defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met. |
6 months
|
|
Phase 2: PFS in participants with solid tumors
기간: 6 months
|
Defined as the interval from the date of the first dose of study treatment until the date of progression of disease or the date of death from any cause, whichever is earlier. |
6 months
|
공동 작업자 및 조사자
수사관
수사관
- 연구 책임자: Mohammed-El-Amine Bensmaine, MD, Incyte Biosciences International Sàrl
간행물 및 유용한 링크
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
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- INCB 84344-102
- 2018 (미국 NIH 보조금/계약)
- 2018-004878-99 (EudraCT 번호)
- 2023-509699-41-00 (레지스트리 식별자: EU CT Number)
- 2023 (미국 NIH 보조금/계약)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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