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Individualized AML Treatment

2026年5月21日 更新者:City of Hope Medical Center

Feasibility Study of Individualized Treatment Recommendations for Acute Myeloid Leukemia Based on High Throughput Screening and Genomics Data

Every patient responds differently to their cancer treatment, and some treatments work better for some patients more than others. For patients with relapsed, refractory ( R/R) AML, there may be fewer approved treatment options remaining. In this research study, the investigators are testing whether high throughput drug screening (HTS) in combination with robust molecular testing by HopeSeq (includes DNA sequencing for >500 genes and 160 gene rearrangements and RNAseq for >5,000 genes) can help doctors determine which treatment might work best for each individual patient. HTS tests how the patient's own AML cells respond to different treatment options including individual drugs and triple drug regimens and recommends for the best treatment options for an individual patient. Participants will provide extra bone marrow and/or blood at the time of routine procedure, and these extra sample(s) will be tested using the Cancer Drug Sensitivity Test ( CDST) HTS, CLIA approved in Washington state since 2014. A committee (the Functional Molecular Tumor Board) will review the HopeSeq and HTS results, past treatments, and clinical description, and give a recommendation for the best AML treatment options for each individual patient. The patient's doctor will get a copy of the recommendation and discuss treatment options with the patient. The patient and their doctor will decide on the best treatment plan for the patient, one which will be approved by insurance. Patients will not be treated with any drugs as part of this study. Then at 6 and 12 months, there will be retrospective review of medical records to determine how will the testing predicted the response, drug sensitivity or resistance, and overall and disease-free survival will be monitored.

調査の概要

詳細な説明

The investigators will utilize high throughput drug screening (HTS) to assess sensitivity of patient's leukemic cells to drugs and drug combinations (~1350). Bone marrow aspirate (BMA) or peripheral blood blasts, or if these are not involved, then bone marrow or tissue biopsy or involved fluids will be used for testing in the HTS and time to HTS report will be recorded. Genomics analysis (sequencing) will be utilized to additionally inform drug choice using the City of Hope HopeSeq Heme Comprehensive (HopeSeq) targeted next generation sequencing (NGS) and RNA seq assays. The turnaround time (TAT) of the above NGS assays is 8-10 business days (≈12-14 calendar days). The Cancer Drug Sensitivity Test Diagnostic (CDST) is a HTS assay with a faster TAT (5-7 calendar days) that is CLIA-approved for patient diagnostic purposes. CDST HTS will be performed in the Quellos High Throughput Core Facility at the University of Washington (UW) in Seattle, WA. These assays detect relevant genomic, and transcriptomic, and functional data events which the investigators hypothesize will provide an opportunity to rationally tailor drug selections and combinations for the treatment of patients with AML that have relapsed and/or refractory AML. HopeSeq, which includes most of the relevant genomic pathways in hematologic malignancies, will be performed on peripheral blood (PB) or bone marrow aspirate (BMA), or if insufficient cells, formalin fixed paraffin embedded (FFPE) tissues may also be analyzed. HopeSeq will be performed as conventional care ~14 days prior to, or at the time of study enrollment, or study will access the results through the Hematopoietic Tissue Biorepository (HTB) at City of Hope. Based on the molecular diagnosis report from HopeSeq and the CDST HTS report, the investigators A propose to convene a Functional Molecular Tumor Board (FMTB) will meet that will consider the data from the molecular and functional studies, as well as information from a literature review for clinical and laboratory findings for other patients with the specific clinical features and molecular/functional data that will offer patients and their physicians treatment recommendations possible treatment options based on multiomic data (HopeSeq and CDST HTS reports) as well as clinical features within 14-18 days from sample acquisition. But ultimately, the patient's treating physician will decide which regimen is best considering individual patient factors such as performance status, prior regimens, insurance authorization, and patient preferences. The retrospective correlation with patient response will enable determination of the relative predictive contribution of each of the tests, both positive and negative predictive value.

研究の種類

観察的

入学 (推定)

18

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

  • 名前:Pamela Becker, MD
  • 電話番号:626-218-2405
  • メールpbecker@coh.org

研究場所

    • California
      • Duarte、California、アメリカ、91010
        • 募集
        • City of Hope Medical Center
        • コンタクト:
          • Pamela Becker, MD
          • 電話番号:626-218-2405
          • メールpbecker@coh.org

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

サンプリング方法

非確率サンプル

調査対象母集団

Adults with relapsed/refractory acute myeloid leukemia

説明

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative.
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  • Age: ≥ 18 years
  • ECOG ≤ 3 (Appendix A)
  • Patients with histologically confirmed AML according to ICC or WHO criteria, and
  • Refractory/relapsed (R/R) to prior treatment with one or more regimens if adverse risk or two or more regimens if favorable/intermediate risk (Appendix B)
  • Sufficient bone marrow and/or peripheral blood sample (archival or fresh) to run the high throughput screening (HTS; Estimate sufficient if circulating blast count of 5,000 or greater or cellular marrow with greater than or equal to 20% blasts.) Otherwise,
  • Sufficient cells flushed from bone marrow biopsy, if bone marrow is not aspirable, OR
  • Extramedullary disease, if it is possible to obtain a fluid or biopsy sample from that location
  • Expected survival is greater than 100 days.
  • Fully recovered from the acute toxic effects (except alopecia) to ≤ Grade 1 to prior anti-cancer therapy

Exclusion Criteria:

  • Treatment with any chemotherapeutic agent necessary to control AML burden is permitted between day -18 and -1.
  • Must not have received or planning to receive live vaccine while being on study
  • Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (FAB class M3-AML)
  • Active central nervous system (CNS) disease (OK if treated and responding)
  • Active graft vs host disease (GVHD)
  • Unstable cardiac disease as defined by one of the following:
  • Cardiac events such as myocardial infarction (MI) within the past 6 months
  • Uncontrolled atrial fibrillation or hypertension
  • Clinically significant uncontrolled illness
  • Uncontrolled active infection
  • Females only: Pregnant or breastfeeding
  • Any other condition or active malignancy that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

コホートと介入

グループ/コホート
介入・治療
R/R AML
Adults with relapsed/refractory acute myeloid leukemia
This is a non-interventional study

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Feasibility - Obtaining HopeSeq and CDST
時間枠:Up to 18 days after sample acquisition

Success in obtaining HopeSeq Heme Comprehensive (HopeSeq) and Cancer Drug Sensitivity Test Diagnostic (CDST) High Throughput Screen (HTS) reports and interpretation of results by the Functional Molecular Tumor Board (FMTB)

Success of performing HOPESEQ and CDST HTS and obtaining an individualized treatment recommendation from the FMTB based on multiomic data within 18 days from sample acquisition.

Up to 18 days after sample acquisition

二次結果の測定

結果測定
メジャーの説明
時間枠
Proportion of participants with successful CDST HTS reports
時間枠:Up to 18 days of sample acquisition

Samples received with sufficient cell numbers and viability to perform CDST HTS

Success of performing HOPESEQ and CDST HTS and obtaining an individualized treatment recommendation from the FMTB based on multiomic data within 18 days from sample acquisition in at least 70% of participants.

Up to 18 days of sample acquisition
Proportion of patients with successful initiation of treatment
時間枠:Up to 1 year
Successful initiation of treatment
Up to 1 year
Average time to successful initiation of treatment
時間枠:Up to 1 year
Time from sample acquisition to successful initiation of treatment
Up to 1 year
Degree of cytoreduction
時間枠:Up to 2-5 weeks after treatment
Bone marrow percent cellularity and percent leukemia by morphology and flow cytometry compared to pre-treatment level
Up to 2-5 weeks after treatment
Preliminary estimate of remission
時間枠:Up to 1 year

Response, duration of remission, time to next treatment as compared to prior interval with most recent treatment, ability to proceed to transplant

Using AML Risk Stratification Criteria by Genetics at Initial Diagnosis from Dohner et al. (2022)

Up to 1 year
Overall survival (OS) and progression-free survival (PFS)
時間枠:Up to 1 year

Day 1 to date of death (OS) or relapse/death (PFS) or last follow up, whichever comes first

Overall survival (OS) and progression-free survival (PFS) will be assessed using the Kaplan-Meier product-limit method, with the median and 95% CI estimated.

Up to 1 year

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

捜査官

  • 主任研究者:Pamela Becker, MD、City of Hope Medical Center

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2026年1月1日

一次修了 (推定)

2027年12月31日

研究の完了 (推定)

2028年6月1日

試験登録日

最初に提出

2026年5月18日

QC基準を満たした最初の提出物

2026年5月21日

最初の投稿 (実際)

2026年5月29日

学習記録の更新

投稿された最後の更新 (実際)

2026年5月29日

QC基準を満たした最後の更新が送信されました

2026年5月21日

最終確認日

2026年5月1日

詳しくは

本研究に関する用語

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

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米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

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