2025-521390-14-00尚未招募2 期
Revumenib Treatment in Combination with FLA Chemotherapy in Paediatric Refractory/Relapsed KMT2A-r, NUP98-r or NPM1-mut Acute Myeloid Leukemia (AML)
GPHS Deutsche Paediatrisch-haematologische Studiengesellschaft mbH2 个研究点 分布在 1 个国家目标入组 2 人开始时间: 2026年2月16日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- The primary efficacy endpoint of Part I in this study is to estimate the ORR. We will compare the ORR to a historically informed null ORR rate of 37% after up to 2 cycles with revumenib in combination with FLA in R/R KMT2A-r, NUP98-r or NPM1- mut AML.
研究概览
简要总结
To estimate the overall response rate (ORR) according to pediatric specific response criteria (Ped- morph-CR/CRi/CRp) after up to 2 cycles with revumenib in combination with FLA in patients with refractory/relapsed (R/R) KMT2A-r, NUP98-r or NPM1-mut AML
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Patients must be > 30 days and ≤ 18 years of age at time of enrollment.
- •Patients must have a performance status ≥50% Lansky or Karnofsky score.
- •Patients may have status of CNS1, CNS2, CNS3 disease without clinical signs or neurologic symptoms suggestive of CNS leukemia, such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome.
- •Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
- •Patients must have adequate renal, liver and cardiac function
- •Patients must have R/R KMT2A-translocation (KMT2A-r), NUP98-rearrangement (NUP98-r) or NPM1-mutation (NPM1-mut AML). History of known KMT2A-r, NUP98-r or NPM1-mut is sufficient. Definition of refractory/relapsed disease (patient must have one of the following): primary refractory disease (≥ 5% leukemic blasts) after 2 cycles of induction, or first recurrent disease (≥ 5% leukemic blasts) after having achieved remission (ped-morph-CR).
- •≥21 days must have elapsed since the patient’s last prior anti-cancer therapy (e.g., chemotherapy), except for protocol-defined pre-phase treatment, which is permitted regardless of the timing.
- •≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without TBI) or boost infusion (any stem cell product; not including DLI); No evidence of graft versus host disease (GVHD) with the exception of Grade 1 skin GVHD being treated by topical treatment.
- •Cellular Therapy: ≥ 28 days after the completion of DLI (donor lymphocyte infusion) or any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.).
- •Understand and voluntarily provide written permission of parental/legal representative(s) to the ICF prior to conducting any trial related assessments/procedures, also concerning data and biomaterial transfer according to ICH/GCP and national/local regulations.
- •Able to adhere to the trial visit schedule and other protocol requirements.
- •Negative serum pregnancy tests for females of child-bearing potential within 10 days prior to treatment.
- •White Blood Cell (WBC): Count must be < 25.000/µL prior to enrolment. Patients may receive cytoreduction with hydroxyurea or low-dose cytarabine (max. 100mg/m² per day) prior to enrollment.
排除标准
- •Patients with isolated extramedullary disease.
- •Patients who are currently receiving another investigational drug.
- •Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant. Patients with active GVHD (other than Grade 1 skin GVHD).
- •Patients who are receiving any strong CYP3A4 inhibitors other than itraconazole, ketoconazole, posaconazole, or voriconazole.
- •Patients who are receiving any strong or moderate CYP3A4 inducers while on study or within 14 days of starting revumenib.
- •Patients who are receiving medications known to prolong the QT/QTc interval (exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies, e.g, diphenhydramine, famotidine, granisetron).
- •Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome.
- •Female patients who are pregnant or breastfeeding.
- •Patients who have ever used revumenib or any other menin inhibitor.
- •Female and male subjects with child bearing potential who avoid using highly effective anticonceptive measure(ment)s.
- •Patients whose baseline QTcF >450ms.
- •Hypersensitivity or allergy to the active substance or other excipients contained in the investigational medical product listed in the Summary of Product Characteristics (SmPC) or Investigators Brochure (IB).
- •Patients with documented active, uncontrolled infection at the time of study entry.
- •Patients with Down Syndrome.
- •Patients with a secondary KMT2A-R, NPM1 or NUP98-r leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy.
- •Patients with known partial duplication of KMT2A (MLL-PTD).
- •Patients with known Mixed Lineage Leukemia.
- •Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrhythmia in the past 6 months prior to study enrolment.
- •Patients with gastrointestinal issues of the upper gastrointestinal tract that might affect oral drug absorption.
结局指标
主要结局
The primary efficacy endpoint of Part I in this study is to estimate the ORR. We will compare the ORR to a historically informed null ORR rate of 37% after up to 2 cycles with revumenib in combination with FLA in R/R KMT2A-r, NUP98-r or NPM1- mut AML.
The primary efficacy endpoint of Part I in this study is to estimate the ORR. We will compare the ORR to a historically informed null ORR rate of 37% after up to 2 cycles with revumenib in combination with FLA in R/R KMT2A-r, NUP98-r or NPM1- mut AML.
次要结局
未报告次要终点
研究者
Kristian Juul-Dam, MD, PhD
Scientific
GPHS Deutsche Paediatrisch-haematologische Studiengesellschaft mbH
研究点 (2)
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