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This is a prospective, multicenter study conducted within the Chinese Children's Cancer Group (CCCG). The study aims to evaluate whether the addition of three novel agents, dasatinib, venetoclax and homoharringtonine, can improve the minimal residual disease (MRD)-negative remission rate, enhance event-free survival (EFS), and reduce the cumulative incidence of relapse (CIR) in pediatric patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL).
The CCCG-T-ALL-2025 protocol will be modified as following based on the above analysis of the CCCG-ALL-2020 protocol.
2.11.7 In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility.
2.11.8 Add drug sensitivity testing for T-ALL.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| (near)ETP-ALL | Experimental | All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in induction therapy. CAT will replace CAT+ during early intensification. Venetoclax will replace daunorubicin in interim therapy 2 and 4. In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility. |
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| nonETP-TALL-Das Group | Experimental | All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy. For non-ETP T-ALL patients with MRD <0.01% on day 46, CAT will replace CAT+ during early intensification, and patients will be continuously subjected to dasatinib combined with chemotherapy during early intensification, interim tharapy, reinduction therapy and maintenance therapy. In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility. |
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| nonETP-TALL-HHT Group | Experimental | All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy. For non-ETP T-ALL patients with MRD ≥0.01% on day 46，CAT+ will be replaced with randomized doses of homoharringtonine (HHT) during early intensification, and HHT will be administrated during reinduction therapy. In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Venetoclax | Drug | All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in induction therapy. CAT will replace CAT+ during early intensification. Venetoclax will replace daunorubicin in interim therapy 2 and 4. In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility. |
| Measure | Description | Time Frame |
|---|---|---|
| End-of-induction(EOI) measurable residual diseases (MRD)-negativity rate in patients with non-ETP T-ALL treated with dasatinib plus 4-drug induction compared to those treated with 4-drug induction in CCCG-ALL-2020 | For this objective a one-sided comparison of probabilities (proportions) will be made. Let p1 and p2 be the probability of aciieving negative EOI MRD on the CCCG-ALL-2020 (historical control) and the current study respectively, then the one-sided alternative hypothesis H0: p2=p1 vs. H1: p2>p1 will be tested. The procedure of two-sample comparison of proportions with the Z-statistic (Normal approximation) will be applied. The current CCCG-ALL2020 data show that among 573 evaluable patients 510 (89%) achaived negative EOI MRD. Benchmarking on these as historical data, a total sample size of n=550 and interim sample size n1=300 provides sufficient popwer for the planned analyses outlined above if the true MRD negativity probability is 0.92 or higher, as shown in the table below. An interim analysis at n1=300 evaluable patients will be conducted for possible abstract submission or publication. | The expected study duration is approximately 5 years. |
| For non-ETP T-ALL patients with positive measurable residual diseases (MRD) on day 46, to compare MRD-negativity rate before consolidation between those receiving single agent homoharringtonine at dose of 1mg/m2 vs. 2mg/m2 for 7 days | The comparison will be condicted by testing the two-sided hypothesis H0: p1=p2 vs. H1: p1≠p2, using the Z test (normal approximation) at alpha=0.10 level. The investigators anticipate approximately 40 patients available to be randomized. The participants will be randomized at 1:1 ratio into the two treatment arms, with 20 patients per arm. Stratified block-wise randomization will be applied with block size of 4. The randomization will be stratified by the EOI MRD level as <1% and >=1%. | The expected study duration is approximately 5 years. |
| End of induction (EOI) measurable residual diseases (MRD)-negativity rate with venetoclax plus 3-drug induction, compared to those treated with 4-drug induction on CCCG-ALL-2020 in treating ETP/near-ETP T-ALL. | The investigators anticipate at least 60 evaluable ETP participants. The analysis will be conducted by testing H0: p2=p1 vs. H1: p2>p1, where p1, p2 are MRD-negative probabilities in the CCCG-ALL-2020 and the current study respectively. The Z-statistic (normal approximation) based procedure will be applied. |
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival (EFS) of patients treated with this therapy, in comparison to historical regimens. | The EFS functions will be estimated by the Kaplan-Meier method along with 95% confidence intervals at specified timepoints (e.g., 1, 3, 5 years since diagnosis). Standard error will be estimated using the default procedure in R. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of EFS will be performed using two-sided log-rank test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Cox models. |
| Measure | Description | Time Frame |
|---|---|---|
| To explore the pharmacokinetic profiles of bioavailability for homoharringtonine and venetoclax with Peak Plasma Concentration (Cmax) | To interpret drug bioavailability, Peak Plasma Concentration (Cmax) will be calculated to qualifies the maximum exposure of the body to the drug overtime . Descriptive statistics (e.g., mean, standard deviation, five-number summary) are used to summarize the data, while visualizations like box plots and line graphs are employed to depict the drug's behavior in the body. It is recommended that centers with the appropriate resources and interest consider undertaking these studies. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jingliao Zhang, MD | Contact | +86 22 23909196 | zhangjingliao@ihcams.ac.cn | |
| Xiaofan Zhu, MD | Contact | + 86 22 23909001 | xfzhu@ihcams.ac.cn |
| Name | Affiliation | Role |
|---|---|---|
| Xiaofan Zhu, MD | Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anhui Medical University Second Affiliated Hospital | Not yet recruiting | Hefei | Anhui | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35271306 | Background | Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. doi: 10.1200/JCO.21.02678. Epub 2022 Mar 10. | |
| 37487146 |
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| ID | Type | URL | Comment |
|---|---|---|---|
| CCCG-ALL | Individual Participant Data Set | View IPD |
IPD will be made available upon publication of the primary trial results or after trial completion, whichever occurs first, starting on 2032, and will remain accessible for 5 years.
Researchers, healthcare professionals who meet the criteria for access (e.g., academic researchers conducting secondary analyses or regulatory bodies reviewing safety data) will be able to request access to de-identified IPD and supporting information. Access will be facilitated through clinical trials.gov/emailing to PI, where users can submit a request and provide a research proposal. Data access will be granted after a formal review and approval process, subject to compliance with the data-sharing agreement and confidentiality terms.
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| Dasatinib | Drug | All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy. For non-ETP T-ALL patients with MRD <0.01% on day 46, CAT will replace CAT+ during early intensification, and patients will be continuously subjected to dasatinib combined with chemotherapy during early intensification, interim tharapy, reinduction therapy and maintenance therapy. In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility. |
|
|
| homoharringtonine | Drug | All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy. For non-ETP T-ALL patients with MRD ≥0.01% on day 46，CAT+ will be replaced with randomized doses of homoharringtonine (HHT) during early intensification, and HHT will be administrated during reinduction therapy. In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility. |
|
|
| The expected study duration is approximately 5 years. |
| In interim therapies 2 and 4, venetoclax replaced daunorubicin to evaluate whether this change could improve event-free survival compared to similar patients on CCCG-ALL-2020 in treating ETP/near-ETP T-ALL. | The investigators anticipate at least 60 evaluable participants. The event-free survival function will be estimated by the Kaplan-Meier method. Comparison will be conducted using the two-sided log-rank test. | The expected study duration is approximately 5 years. |
| Approximately 6.5 years. |
| Overall survival (OS) of patients treated with this therapy, in comparison to historical regimens | The OS functions will be estimated by the Kaplan-Meier method along with 95% confidence intervals at specified timepoints (e.g., 1, 3, 5 years since diagnosis). Comparison of OS functions will be conducted using the two-sided log-rank test. Standard error will be estimated using the default procedure in R. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of OS will be performed using two-sided log-rank test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Cox models. | Approximately 6.5 years. |
| Cumulative incidence of relapse (CIR) of this therapy, in comparison to historical regimens. | CIR functions of relapse will be estimated by the Kalbafleisch-Prentice method. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of CIR will be performed by Gray's test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Fine-Gray models. | Approximately 6.5 years. |
| Incidence of Grade 4 Treatment-Emergent Adverse Events (TEAE) associated with venetoclax and homoharringtonine | Proportions of grade-4 TEAEs in each treatment phase will be estimated by the sample proportions along with exact 95% confidence intervals. Cumulative incidences of various grade-3 or higher AEs throughout therapy will be estimated by the Kalbafleisch-Prentice method; death, relapse and other events rendering off therapy before completion are regarded as competing risks. | Up to 30 days after last dose of study treatment |
| Up to 30 days after last dose of study drug administration |
| To explore the pharmacokinetic profiles of bioavailability for homoharringtonine and venetoclax with Area Under the Plasma Concentration-Time Curve (AUC) | To interpret drug bioavailability, Area Under the Plasma Concentration-Time Curve (AUC) will be calculated to qualifies the total exposure of the body to the drug overtime . Descriptive statistics (e.g., mean, standard deviation, five-number summary) are used to summarize the data, while visualizations like box plots and line graphs are employed to depict the drug's behavior in the body. It is recommended that centers with the appropriate resources and interest consider undertaking these studies. | Up to 30 days after last dose of study drug administration |
| To explore the pharmacokinetic profiles of absorbance duration for homoharringtonine and venetoclax with Time to Peak Concentration (Tmax) | To understand how soon of drug absorbance duration, Time to Peak Concentration (Tmax) will be analyzed. Comprehensive descriptive statistics (e.g., mean, standard deviation, five-number summary) are used to summarize the data, while visualizations like box plots and line graphs are employed to depict the drug's behavior in the body. It is recommended that centers with the appropriate resources and interest consider undertaking these studies. | Up to 30 days after last dose of study drug administration |
| To explore the pharmacokinetic profiles of absorbance duration for homoharringtonine and venetoclax with Clearance (Cl) | To understand how efficiently the body eliminates the drug , Clearance (CI) will be analyzed to calculate the volume of plasma from which the drug is completely removed per unit of time. Comprehensive descriptive statistics (e.g., mean, standard deviation, five-number summary) are used to summarize the data, while visualizations like box plots and line graphs are employed to depict the drug's behavior in the body. It is recommended that centers with the appropriate resources and interest consider undertaking these studies. | Up to 30 days after last dose of study drug administration |
| To explore the pharmacodynamic profiles of homoharringtonine and venetoclax. | To outline the therapeutic effects from pharmarcotyping experiments, parameters as EC50 (the concentration of drug at which 50% of the maximal effect is observed) will be calculated from the dose-response curve. Visualizations as dose-response curves and concentration-effect curves are employed to depict the drug's efficacy against concentration. It is recommended that centers with the appropriate resources and interest consider undertaking these studies. | Up to 30 days after last dose of study drug administration |
| Anhui Provincial Children's Hospital | Not yet recruiting | Hefei | Anhui | China |
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| Chongqing Medical University Affiliated Children's Hospital | Not yet recruiting | Chongqing | Chongqing Municipality | China |
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| Fujian Medical University Union Hospital | Not yet recruiting | Fuzhou | Fujian | China |
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| Guangzhou Women and Children's Medical Center | Not yet recruiting | Guangzhou | Guangdong | China |
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| Nanfang Hospital, Southern Medical University | Not yet recruiting | Guangzhou | Guangdong | China |
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| The People's Hospital of Guangxi Zhuang Autonomous Region | Not yet recruiting | Nanning | Guangxi | China |
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| The Affiliated Hospital of Guizhou Medical University | Not yet recruiting | Guiyang | Guizhou | China |
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| Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology | Not yet recruiting | Wuhan | Hubei | China |
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| Union Hospital of Tongji Medical College, Huazhong University of Science and Technology | Not yet recruiting | Wuhan | Hubei | China |
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| Wuhan Children's Hospital | Not yet recruiting | Wuhan | Hubei | China |
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| Hunan Children's Hospital | Not yet recruiting | Changsha | Hunan | China |
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| The Third Xiangya Hospital of the Central South University | Not yet recruiting | Changsha | Hunan | China |
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| Xiangya Hospital Central South University | Not yet recruiting | Changsha | Hunan | China |
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| Nanjing Children's Hospital Affiliated to Nanjing Medical University | Not yet recruiting | Nanjin | Jiangsu | China |
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| Children's Hospital of Soochow University | Not yet recruiting | Suzhou | Jiangsu | China |
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| Jiangxi Provincial Children's Hospital | Not yet recruiting | Nanchang | Jiangxi | China |
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| Qilu Hospital of Shandong University | Not yet recruiting | Jinan | Shandong | China |
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| Affiliated Hospital of Qingdao University | Not yet recruiting | Qingdao | Shandong | China |
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| Children's Hospital of Fudan University | Not yet recruiting | Shanghai | Shanghai Municipality | China |
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| Shanghai Children's Hospital | Not yet recruiting | Shanghai | Shanghai Municipality | China |
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| Shanghai Children's Medical Cener, Shanghai Jiao Tong University School of Medicine | Not yet recruiting | Shanghai | Shanghai Municipality | China |
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| Xi'an Northwest Women and Children Hospital | Not yet recruiting | Xi’an | Shanxi | China |
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| Shenzhen Children's Hospital | Not yet recruiting | Shenzhen | Shenzhen | China |
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| West China Second University Hospital | Not yet recruiting | Chengdu | Sichuan | China |
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| Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC | Recruiting | Tianjin | Tianjin Municipality | China |
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| Hong Kong Children's Hospital | Not yet recruiting | Hong Kong | Hong Kong | Hong Kong |
|
| Background |
| Raetz EA, Rebora P, Conter V, Schrappe M, Devidas M, Escherich G, Imai C, De Moerloose B, Schmiegelow K, Burns MA, Elitzur S, Pieters R, Attarbaschi A, Yeoh A, Pui CH, Stary J, Cario G, Bodmer N, Moorman AV, Buldini B, Vora A, Valsecchi MG. Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials. J Clin Oncol. 2023 Nov 10;41(32):5025-5034. doi: 10.1200/JCO.23.00088. Epub 2023 Jul 24. |
| 39143224 | Background | Polonen P, Di Giacomo D, Seffernick AE, Elsayed A, Kimura S, Benini F, Montefiori LE, Wood BL, Xu J, Chen C, Cheng Z, Newman H, Myers J, Iacobucci I, Li E, Sussman J, Hedges D, Hui Y, Diorio C, Uppuluri L, Frank D, Fan Y, Chang Y, Meshinchi S, Ries R, Shraim R, Li A, Bernt KM, Devidas M, Winter SS, Dunsmore KP, Inaba H, Carroll WL, Ramirez NC, Phillips AH, Kriwacki RW, Yang JJ, Vincent TL, Zhao Y, Ghate PS, Wang J, Reilly C, Zhou X, Sanders MA, Takita J, Kato M, Takasugi N, Chang BH, Press RD, Loh M, Rampersaud E, Raetz E, Hunger SP, Tan K, Chang TC, Wu G, Pounds SB, Mullighan CG, Teachey DT. The genomic basis of childhood T-lineage acute lymphoblastic leukaemia. Nature. 2024 Aug;632(8027):1082-1091. doi: 10.1038/s41586-024-07807-0. Epub 2024 Aug 14. |
| 35441457 | Background | He Y, Zhang J, Zhang Y, Hu Z, Wang P, Gan W, Xie S, Qian M, Pui CH, Jiang H, Zhu X, Zhang H, Zhang W. Dasatinib-therapy induced sustained remission in a child with refractory TCF7-SPI1 T-cell acute lymphoblastic leukemia. Pediatr Blood Cancer. 2022 Aug;69(8):e29724. doi: 10.1002/pbc.29724. Epub 2022 Apr 20. |
| 38848537 | Background | Simonin M, Vasseur L, Lengline E, Lhermitte L, Cabannes-Hamy A, Balsat M, Schmidt A, Dourthe ME, Touzart A, Graux C, Grardel N, Cayuela JM, Arnoux I, Gandemer V, Huguet F, Ducassou S, Lheritier V, Chalandon Y, Ifrah N, Dombret H, Macintyre E, Petit A, Rousselot P, Lambert J, Baruchel A, Boissel N, Asnafi V. NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of patients. Blood. 2024 Oct 10;144(15):1570-1580. doi: 10.1182/blood.2023023754. |
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| 21719599 | Background | Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grumayer R, Moricke A, Parasole R, Zimmermann M, Dworzak M, Buldini B, Reiter A, Basso G, Klingebiel T, Messina C, Ratei R, Cazzaniga G, Koehler R, Locatelli F, Schafer BW, Arico M, Welte K, van Dongen JJ, Gadner H, Biondi A, Conter V. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011 Aug 25;118(8):2077-84. doi: 10.1182/blood-2011-03-338707. Epub 2011 Jun 30. |
| 38968151 | Background | Suo S, Zhao D, Li F, Zhang Y, Rodriguez-Rodriguez S, Nguyen LXT, Ghoda L, Carlesso N, Marcucci G, Zhang B, Jin J. Homoharringtonine inhibits the NOTCH/MYC pathway and exhibits antitumor effects in T-cell acute lymphoblastic leukemia. Blood. 2024 Sep 19;144(12):1343-1347. doi: 10.1182/blood.2023023400. |
| 20971952 | Background | Chen R, Guo L, Chen Y, Jiang Y, Wierda WG, Plunkett W. Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia. Blood. 2011 Jan 6;117(1):156-64. doi: 10.1182/blood-2010-01-262808. Epub 2010 Oct 22. |
| 30659143 | Background | Chen XJ, Zhang WN, Chen B, Xi WD, Lu Y, Huang JY, Wang YY, Long J, Wu SF, Zhang YX, Wang S, Li SX, Yin T, Lu M, Xi XD, Li JM, Wang KK, Chen Z, Chen SJ. Homoharringtonine deregulates MYC transcriptional expression by directly binding NF-kappaB repressing factor. Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2220-2225. doi: 10.1073/pnas.1818539116. Epub 2019 Jan 18. |
| 24387717 | Background | Lu S, Wang J. Homoharringtonine and omacetaxine for myeloid hematological malignancies. J Hematol Oncol. 2014 Jan 3;7:2. doi: 10.1186/1756-8722-7-2. |
| 37363966 | Background | Saygin C, Giordano G, Shimamoto K, Eisfelder B, Thomas-Toth A, Venkataraman G, Ananthanarayanan V, Vincent TL, DuVall A, Patel AA, Chen Y, Tan F, Anthony SP, Chen Y, Shen Y, Odenike O, Teachey DT, Kee BL, LaBelle J, Stock W. Dual Targeting of Apoptotic and Signaling Pathways in T-Lineage Acute Lymphoblastic Leukemia. Clin Cancer Res. 2023 Aug 15;29(16):3151-3161. doi: 10.1158/1078-0432.CCR-23-0415. |
| 32139432 | Background | Shi Y, Beckett MC, Blair HJ, Tirtakusuma R, Nakjang S, Enshaei A, Halsey C, Vormoor J, Heidenreich O, Krippner-Heidenreich A, van Delft FW. Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia. Haematologica. 2021 Apr 1;106(4):1056-1066. doi: 10.3324/haematol.2019.241026. |
| 37076694 | Background | Yoshimura S, Panetta JC, Hu J, Li L, Gocho Y, Du G, Umezawa A, Karol SE, Pui CH, Mullighan CG, Konopleva M, Stock W, Teachey DT, Jain N, Yang JJ. Preclinical pharmacokinetic and pharmacodynamic evaluation of dasatinib and ponatinib for the treatment of T-cell acute lymphoblastic leukemia. Leukemia. 2023 Jun;37(6):1194-1203. doi: 10.1038/s41375-023-01900-5. Epub 2023 Apr 19. |
| 34151288 | Background | Gocho Y, Liu J, Hu J, Yang W, Dharia NV, Zhang J, Shi H, Du G, John A, Lin TN, Hunt J, Huang X, Ju B, Rowland L, Shi L, Maxwell D, Smart B, Crews KR, Yang W, Hagiwara K, Zhang Y, Roberts K, Wang H, Jabbour E, Stock W, Eisfelder B, Paietta E, Newman S, Roti G, Litzow M, Easton J, Zhang J, Peng J, Chi H, Pounds S, Relling MV, Inaba H, Zhu X, Kornblau S, Pui CH, Konopleva M, Teachey D, Mullighan CG, Stegmaier K, Evans WE, Yu J, Yang JJ. Network-based systems pharmacology reveals heterogeneity in LCK and BCL2 signaling and therapeutic sensitivity of T-cell acute lymphoblastic leukemia. Nat Cancer. 2021 Mar;2(3):284-299. doi: 10.1038/s43018-020-00167-4. Epub 2021 Jan 21. |
| 36604538 | Background | Lee SHR, Yang W, Gocho Y, John A, Rowland L, Smart B, Williams H, Maxwell D, Hunt J, Yang W, Crews KR, Roberts KG, Jeha S, Cheng C, Karol SE, Relling MV, Rosner GL, Inaba H, Mullighan CG, Pui CH, Evans WE, Yang JJ. Pharmacotypes across the genomic landscape of pediatric acute lymphoblastic leukemia and impact on treatment response. Nat Med. 2023 Jan;29(1):170-179. doi: 10.1038/s41591-022-02112-7. Epub 2023 Jan 5. |
| 24994123 | Background | Chonghaile TN, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, Loh ML, Hunger SP, Wood B, DeAngelo DJ, Stone R, Harris M, Gutierrez A, Kelliher MA, Letai A. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov. 2014 Sep;4(9):1074-87. doi: 10.1158/2159-8290.CD-14-0353. Epub 2014 Jul 3. |
| 37027330 | Background | Borah P, Dayal N, Pathak S, Naithani R. Short-course Venetoclax With Standard Chemotherapy Is Effective in Early T-cell Precursor Acute Lymphoblastic Leukemia. J Pediatr Hematol Oncol. 2023 Jul 1;45(5):271-274. doi: 10.1097/MPH.0000000000002672. Epub 2023 Apr 4. |
| 32035785 | Background | Richard-Carpentier G, Jabbour E, Short NJ, Rausch CR, Savoy JM, Bose P, Yilmaz M, Jain N, Borthakur G, Ohanian M, Alvarado Y, Rytting M, Kebriaei P, Konopleva M, Kantarjian H, Ravandi F. Clinical Experience With Venetoclax Combined With Chemotherapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2020 Apr;20(4):212-218. doi: 10.1016/j.clml.2019.09.608. Epub 2019 Sep 30. |
| 35008312 | Background | Gibson A, Trabal A, McCall D, Khazal S, Toepfer L, Bell DH, Roth M, Mahadeo KM, Nunez C, Short NJ, DiNardo C, Konopleva M, Issa GC, Ravandi F, Jain N, Borthakur G, Kantarjian HM, Jabbour E, Cuglievan B. Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancers (Basel). 2021 Dec 29;14(1):150. doi: 10.3390/cancers14010150. |
| 22649144 | Background | Davids MS, Letai A. Targeting the B-cell lymphoma/leukemia 2 family in cancer. J Clin Oncol. 2012 Sep 1;30(25):3127-35. doi: 10.1200/JCO.2011.37.0981. Epub 2012 May 29. |
| 26888258 | Background | Moricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, Locatelli F, Cazzaniga G, Niggli F, Arico M, Bartram CR, Attarbaschi A, Silvestri D, Beier R, Basso G, Ratei R, Kulozik AE, Lo Nigro L, Kremens B, Greiner J, Parasole R, Harbott J, Caruso R, von Stackelberg A, Barisone E, Rossig C, Conter V, Schrappe M. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016 Apr 28;127(17):2101-12. doi: 10.1182/blood-2015-09-670729. Epub 2016 Feb 17. |
| 37141547 | Background | Campbell M, Kiss C, Zimmermann M, Riccheri C, Kowalczyk J, Felice MS, Kuzmanovic M, Kovacs G, Kosmidis H, Gonzalez A, Bilic E, Castillo L, Kolenova A, Jazbec J, Popa A, Konstantinov D, Kappelmayer J, Szczepanski T, Dworzak M, Buldini B, Gaipa G, Marinov N, Rossi J, Nagy A, Gaspar I, Stary J, Schrappe M. Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia Intercontinental-Berlin-Frankfurt-Munster 2009 Trial. J Clin Oncol. 2023 Jul 1;41(19):3499-3511. doi: 10.1200/JCO.22.01760. Epub 2023 May 4. |
| 24708207 | Background | Patrick K, Wade R, Goulden N, Mitchell C, Moorman AV, Rowntree C, Jenkinson S, Hough R, Vora A. Outcome for children and young people with Early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol. 2014 Aug;166(3):421-4. doi: 10.1111/bjh.12882. Epub 2014 Apr 8. |
| 37556734 | Background | Wood BL, Devidas M, Summers RJ, Chen Z, Asselin B, Rabin KR, Zweidler-McKay PA, Winick NJ, Borowitz MJ, Carroll WL, Raetz EA, Loh ML, Hunger SP, Dunsmore KP, Teachey DT, Winter SS. Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children's Oncology Group study. Blood. 2023 Dec 14;142(24):2069-2078. doi: 10.1182/blood.2023020678. |
| 33639000 | Background | Morita K, Jain N, Kantarjian H, Takahashi K, Fang H, Konopleva M, El Hussein S, Wang F, Short NJ, Maiti A, Sasaki K, Garcia-Manero G, Konoplev S, Ravandi F, Khoury JD, Jabbour E. Outcome of T-cell acute lymphoblastic leukemia/lymphoma: Focus on near-ETP phenotype and differential impact of nelarabine. Am J Hematol. 2021 May 1;96(5):589-598. doi: 10.1002/ajh.26144. Epub 2021 Mar 18. |
| 19147408 | Background | Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, Cheng C, Su X, Rubnitz JE, Basso G, Biondi A, Pui CH, Downing JR, Campana D. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009 Feb;10(2):147-56. doi: 10.1016/S1470-2045(08)70314-0. Epub 2009 Jan 13. |
| 28671688 | Background | Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, McCastlain K, Edmonson M, Pounds SB, Shi L, Zhou X, Ma X, Sioson E, Li Y, Rusch M, Gupta P, Pei D, Cheng C, Smith MA, Guidry Auvil JM, Gerhard DS, Relling MV, Winick NJ, Carroll AJ, Heerema NA, Raetz E, Devidas M, Willman CL, Harvey RC, Carroll WL, Dunsmore KP, Winter SS, Wood BL, Sorrentino BP, Downing JR, Loh ML, Hunger SP, Zhang J, Mullighan CG. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017 Aug;49(8):1211-1218. doi: 10.1038/ng.3909. Epub 2017 Jul 3. |
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CCCG-ALL-2025 DATASET |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D054218 | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C579720 | venetoclax |
| D001215 | Asparaginase |
| D014750 | Vincristine |
| D003561 | Cytarabine |
| D008727 | Methotrexate |
| D003630 | Daunorubicin |
| D003907 | Dexamethasone |
| D000069439 | Dasatinib |
| D000077863 | Homoharringtonine |
| ID | Term |
|---|---|
| D000581 | Amidohydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D013259 | Steroids, Fluorinated |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
| D006248 | Harringtonines |
| D001552 | Benzazepines |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
Not provided
Not provided