Newly-diagnosed Pediatric T-cell ALL Protocol (CCCG-TALL-2025)

August 23, 2025 updated by: Institute of Hematology & Blood Diseases Hospital, China

Chinese Children's Cancer Group T-cell Acute Lymphoblastic Leukemia -2025 Project

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The CCCG-T-ALL-2025 protocol will be modified as following based on the above analysis of the CCCG-ALL-2020 protocol.

  1. All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy.
  2. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy.
  3. non-ETP T-ALL patients with MRD ≥ 0.01% on day 46 will be stratified and randomized to receive different doses of homoharringtonine during early intensification.
  4. For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in induction therapy.
  5. For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in interim therapy 2 and 4.
  6. CAT will replace CAT+ during early intensification, and will be administrated to all ETP/near-ETP patients, as well as non-ETP patients with MRD< 0.01% on day 46.

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.

Study Type

Interventional

Enrollment (Estimated)

610

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China
        • Not yet recruiting
        • Anhui Provincial Children's Hospital
        • Contact:
          • Xuhan Zhang, PhD
          • Phone Number: 0551-62284005
      • Hefei, Anhui, China
        • Not yet recruiting
        • Anhui Medical University Second Affiliated Hospital
        • Contact:
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China
        • Not yet recruiting
        • Chongqing Medical University Affiliated Children's Hospital
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • Fujian Medical University Union Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Nanfang Hospital, Southern Medical University
        • Contact:
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Guangzhou Women and Children's Medical Center
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China
        • Not yet recruiting
        • The People's Hospital of Guangxi Zhuang Autonomous Region
        • Contact:
    • Guizhou
      • Guiyang, Guizhou, China
        • Not yet recruiting
        • The Affiliated Hospital of Guizhou Medical University
        • Contact:
    • Hubei
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Wuhan Children's Hospital
        • Contact:
    • Hunan
      • Changsha, Hunan, China
        • Not yet recruiting
        • Xiangya Hospital Central South University
        • Contact:
      • Changsha, Hunan, China
        • Not yet recruiting
        • Hunan Children's Hospital
        • Contact:
      • Changsha, Hunan, China
        • Not yet recruiting
        • The Third Xiangya Hospital of the Central South University
        • Contact:
    • Jiangsu
      • Nanjin, Jiangsu, China
        • Not yet recruiting
        • Nanjing Children's Hospital Affiliated to Nanjing Medical University
        • Contact:
          • Yongjun Fang, MD
          • Phone Number: 025-83117500
          • Email: fyj322@189.cn
      • Suzhou, Jiangsu, China
        • Not yet recruiting
        • Children's Hospital of Soochow University
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China
        • Not yet recruiting
        • Jiangxi Provincial Children's Hospital
        • Contact:
    • Shandong
      • Jinan, Shandong, China
        • Not yet recruiting
        • Qilu Hospital of Shandong University
        • Contact:
      • Qingdao, Shandong, China
        • Not yet recruiting
        • Affiliated Hospital of Qingdao University
        • Contact:
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China
        • Not yet recruiting
        • Children's Hospital of Fudan University
        • Contact:
      • Shanghai, Shanghai Municipality, China
        • Not yet recruiting
        • Shanghai Children's Hospital
        • Contact:
      • Shanghai, Shanghai Municipality, China
        • Not yet recruiting
        • Shanghai Children's Medical Cener, Shanghai Jiao Tong University School of Medicine
        • Contact:
    • Shanxi
      • Xi’an, Shanxi, China
        • Not yet recruiting
        • Xi'an Northwest Women and Children Hospital
        • Contact:
    • Shenzhen
      • Shenzhen, Shenzhen, China
        • Not yet recruiting
        • Shenzhen Children's Hospital
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China
        • Not yet recruiting
        • West China Second University Hospital
        • Contact:
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China
        • Recruiting
        • Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
        • Contact:
  • Hong Kong
    • Hong Kong
      • Hong Kong, Hong Kong, Hong Kong
        • Not yet recruiting
        • Hong Kong Children's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age older than 1 month to younger than 18 years.
  2. Diagnosis of acute lymphoblastic leukemia by bone marrow morphology.
  3. Diagnosis of T-ALL by immunophenotyping.

Exclusion Criteria:

  1. B-ALL
  2. AML
  3. Acute leukemias of ambiguous lineage diagnosed according to WHO or EGIL criteria.
  4. ALL evolved from chronic myeloid leukemia (CML).
  5. Down's syndrome, or major congenital or hereditary disease with organ dysfunction
  6. Secondary leukemia
  7. Known underlying congenital immunodeficiency or metabolic disease
  8. Congenital heart disease with cardiac insufficiency.
  9. Treated with glucocorticoids for ≥14 days, or ABL kinase inhibitors for > 7 days within one month before enrollment, or any chemotherapy or radiotherapy within 3 months before enrollment (except for emergency radiotherapy to relieve airway compression)
  10. Any significant comorbidities or psychiatric disorders that may impact patient safety, compliance, informed consent, study participation, follow-up, or the interpretation of study results. In such cases, all participating sites must report directly to the PI to determine whether the patient meets exclusion criteria.
  11. Severe malnutrition, active infections, heart failure, or chemotherapy intolerance.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: (near)ETP-ALL
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.
Drug: Venetoclax
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.
Other Names:
  • Dexamethasone
  • Cytarabine
  • 6-MP
  • Methotrexate
  • Vincristine
  • Daunorubicin
  • Asparaginase
  • Cyclophosphomide
Experimental: nonETP-TALL-Das Group
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.
Drug: Dasatinib
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.
Other Names:
  • Dexamethasone
  • Cytarabine
  • 6-MP
  • Methotrexate
  • Vincristine
  • Daunorubicin
  • Asparaginase
  • Cyclophosphomide
Experimental: nonETP-TALL-HHT Group
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.
Drug: homoharringtonine
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.
Other Names:
  • Dexamethasone
  • Cytarabine
  • 6-MP
  • Methotrexate
  • Vincristine
  • Daunorubicin
  • Asparaginase
  • Cyclophosphomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: The expected study duration is approximately 5 years.

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.
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.
Time Frame: The expected study duration is approximately 5 years.
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.
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
Time Frame: The expected study duration is approximately 5 years.

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.
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.
Time Frame: The expected study duration is approximately 5 years.
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.
The expected study duration is approximately 5 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS) of patients treated with this therapy, in comparison to historical regimens.
Time Frame: Approximately 6.5 years.
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.
Approximately 6.5 years.
Overall survival (OS) of patients treated with this therapy, in comparison to historical regimens
Time Frame: Approximately 6.5 years.
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.
Time Frame: Approximately 6.5 years.
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
Time Frame: Up to 30 days after last dose of study treatment
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To explore the pharmacokinetic profiles of bioavailability for homoharringtonine and venetoclax with Peak Plasma Concentration (Cmax)
Time Frame: Up to 30 days after last dose of study drug administration
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.
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)
Time Frame: Up to 30 days after last dose of study drug administration
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)
Time Frame: Up to 30 days after last dose of study drug administration
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)
Time Frame: Up to 30 days after last dose of study drug administration
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.
Time Frame: Up to 30 days after last dose of study drug administration
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Investigators

  • Principal Investigator: Xiaofan Zhu, MD, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 11, 2025

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

June 1, 2031

Study Registration Dates

First Submitted

February 4, 2025

First Submitted That Met QC Criteria

February 25, 2025

First Posted (Actual)

March 4, 2025

Study Record Updates

Last Update Posted (Estimated)

August 26, 2025

Last Update Submitted That Met QC Criteria

August 23, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT2025014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

  1. Demographic Data: Age, sex, and other relevant baseline characteristics.
  2. Treatment Information: Data on interventions received by participants, including dosage, treatment cycles, and duration.
  3. Outcome Measures: Detailed information on primary and secondary outcome measures, such as response rates, survival rates, adverse events, and any the pre-specified endpoints.
  4. Adverse Events: Data on all reported adverse events, including severity, duration, and outcome.
  5. Laboratory Data: Results from laboratory tests, such as blood counts, biochemical markers, or molecular analysis.
  6. Medical History: Pre-existing conditions, comorbidities, and prior treatments or interventions.
  7. Vital Signs: relevant physiological data.
  8. Efficacy and Safety Data: Any data relating to the efficacy (e.g., event-free survival) and safety (e.g., adverse effects) of the treatment.

IPD Sharing Time Frame

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.

IPD Sharing Access Criteria

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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: CCCG-ALL
    Information comments: CCCG-ALL-2025 DATASET

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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