NL-OMON53652尚未招募2 期
International proof of concept therapeutic Stratification trial of Molecular Anomalies in Relapsed or Refractory HEMatological malignancies in children. Sub-Protocol D: Trametinib + Dexamethasone + Cyclophosphamide and Cytarabine in pediatric patients with relapsed or refractory hematological malignancies - HEM-iSMART sub-protocol D
Prinses Máxima Centrum voor Kinderoncologie0 个研究点目标入组 3 人开始时间: 待定最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 3
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 0 至 64（—）
入选标准
- •Patients must have any of the conditions (Group A to E) depicted below for
- •being eligible for the trial. Patients need to fulfill all inclusion and
- •exclusion criteria depicted in sections 5.1 and 5.2. T-ALL and T-LBL Cohort:
- •Group A: T-ALL in first or greater relapse/refractory to at least one prior
- •regimen defined as: - >= 5% blasts in the marrow after first line induction and
- •consolidaton blocks or any re-induction therapy for 1st or subsequent
- •relapse(s)/refractoriness OR - Be in complete morphological remission (< 5%
- •blasts in the marrow) but having o MRD >=1 x 10-3 after first line induction and
- •consolidaton blocks, or o >=1 x 10-4 after any re-induction therapy for 1st or
- •subsequent relapse(s)/refractoriness. Group B: T-LBL (histology proven or
- •diagnosed applying flow cytometry and/or cytomorphology of bone marrow (bone
- •marrow blast count >= 5% but < 25 %), peripheral blood and effusions) in
- •first or greater relapse/refractoriness to at least one prior induction regimen
- •defined as: - Evidence of measurable disease by radiological criteria after
- •first line induction and consolidaton blocks or any re-induction therapy for
- •1st or subsequent relapse(s)/refractoriness AND/OR - >= 5% blasts in the marrow
- •after first line induction and consolidaton blocks or any re-induction therapy
- •for 1st or subsequent relapse(s)/refractoriness OR - Be in complete
- •morphological remission (< 5% blasts in the marrow and no extra-medullary
- •disease) but having MRD >= 1 x 10-3 after first line induction and consolidaton
- •blocks or >=1 x 10-4 after any re-induction therapy for 1st or subsequent
- •relapse(s)/refractoriness. Group C: - Patients with either T-ALL or T-LBL who
- •are in complete morphological remission (< 5% blasts in the marrow and no
- •extra-medullary disease) but who have experienced a molecular reappearance
- •defined as *reconversion after minimal residual disease (MRD) negativity* to
- •reproducible MRD positivity (>=1 x 10-4). MRD positivity MUST be confirmed in
- •two different samples in the bone marrow two weeks apart before the enrolment
- •of these patients into the trial or by two independent methods (f.ex. PCR and
- •flow-cytometry) at one measurement. BCP-ALL and B-LL Cohort: These patients can
- •ONLY be enrolled into the dose finding phase (Phase I) of the sub-protocols at
- •the moment. Group D: BCP-ALL in second or greater relapse or refractory to 2
- •prior regimens defined as: - >= 5% blasts in the marrow after any re-induction
- •therapy for 2nd or subsequent relapse(s)/refractoriness OR - Be in complete
- •morphological remission (< 5% blasts in the marrow) but having MRD >= 1 x
- •10-4 after any re-induction therapy for 2nd or subsequent
- •relapse(s)/refractoriness NOTE: Patients with BCP-ALL MUST have received and
- •failed hematopoietic stem cell transplantation (HSCT) and/or CAR-T therapy.
- •Exceptions to this are: absence of a suitable donor, failure of manufacturing
- •CAR-T, impossibility to access a CAR-T-program, patients not candidates to
- •CAR-T-therapy due to clinical reasons. These patients need to be discussed with
- •the sponsor on a single case basis. Group E: B-LBL (histology proven or
- •diagnosed applying flow cytometry and/or cytomorphology of bone marrow (bone
- •marrow blast count >= 5% but < 25 %), peripheral blood and effusions) in
- •first or greater relapse/refractory to
排除标准
- •1. Pregnancy or positive pregnancy test (urine or serum) in females of
- •childbearing potential. Pregnancy test must be performed within 7 days prior to
- •C1D1. 2. Sexually active participants not willing to use highly effective
- •contraceptive method (pearl index <1) as defined in CTFG HMA 2020 (Appendix
- •II) during trial participation and until 6 months after end of antileukemic
- •therapy. 3. Breast feeding. 4. Impairment of gastrointestinal (GI) function or
- •GI disease that may significantly alter drug absorption of oral drugs (e.g.,
- •ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption
- •syndrome) in case of oral IMPs. 5. Have a known immediate or delayed
- •hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs
- •chemically related to study treatment or excipients that contraindicate their
- •participation, including conventional chemotherapeutics (i.e. cytarabine and
- •cyclophosphamide, intrathecal agents) and corticoids. 6. Known active viral
- •hepatitis or known human immunodeficiency virus (HIV) infection or any other
- •uncontrolled infection. 7. Severe concomitant disease that does not allow
- •treatment according to the protocol at the investigator*s discretion. 8.
- •Subjects unwilling or unable to comply with the study procedures. 9. Previous
- •treatment with trametinib. 10. Current use of a prohibited medication or herbal
- •preparation or requires any of these medications during the study. See Section
- •7 and Appendix III for details. Drugs inducing QTc changes (prolongation of the
- •QT interval or inducing Torsade de Points) are not permitted. 11. Unresolved
- •toxicity greater than NCI CTCAE v 5.0 >= grade 2 from previous anti-cancer
- •therapy, including major surgery, except those that in the opinion of the
- •investigator are not clinically relevant given the known safety/toxicity
- •profile of the study treatment (e.g., alopecia and/or peripheral neuropathy
- •related to platinum or vinca alkaloid based chemotherapy) (Common Terminology
- •Criteria for Adverse Events (CTCAE) (cancer.gov). 12. Active acute graft versus
- •host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients
- •receiving any agent to treat or prevent GvHD post bone marrow transplant are
- •not eligible for this trial. 13. Received immunosuppression post allogenic HSCT
- •within one moth of study entry. 14. History or current evidence of retina vein
- •occlusion (RVO) or central serous retinopathy are excluded. 15. Wash-out
- •periods of prior medication: a. CHEMOTHERAPY: At least 7 days must have elapsed
- •since the completion of cytotoxic therapy, with the exception of hydroxyurea,
- •6-mercaptopurine, oral methotrexate and steroids which are permitted up until
- •48 hours prior to initiating protocol therapy. Patients may have received
- •intrathecal therapy (IT) at any time prior to study entry. b. RADIOTHERAPY:
- •Radiotherapy (non-palliative) within 21 days prior to the first dose of drug.
- •Palliative radiation in past 21 days is allowed. c. HEMATOPOIETIC STEM CELL
- •TRANSPLANTATION (HSCT): i. Autologous HSCT within 2 months prior to the first
- •study drug dose. ii. Allogeneic HSCT within 3 months prior to the first study
- •drug dose. d. IMMUNOTHERAPY: At least 42 days must have elapsed after the
- •completion of any type of immunotherapy other than monoclonal antibodies (e.g.
- •Inotuzumab) e. MONOCLONAL A
研究者
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