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NCT Number: NCT06855810

Newly-diagnosed Pediatric T-cell ALL Protocol

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).

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Key information

Conditions

Acute Lymphoblastic Leukemia Childhood Leukemia, Acute Lymphoblastic Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

Age range

1 month–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Anhui Medical University Second Affiliated Hospital, Hefei, Anhui, China

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About this study

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

  • 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.
  • 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.
  • For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in induction therapy.
  • For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in interim therapy 2 and 4.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • B-ALL
  • AML
  • Acute leukemias of ambiguous lineage diagnosed according to WHO or EGIL criteria.
  • ALL evolved from chronic myeloid leukemia (CML).
  • Down's syndrome, or major congenital or hereditary disease with organ dysfunction
  • Secondary leukemia
  • Known underlying congenital immunodeficiency or metabolic disease
  • Congenital heart disease with cardiac insufficiency.
  • 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)
  • 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.
  • Severe malnutrition, active infections, heart failure, or chemotherapy intolerance.

Treatment and study plan

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.

Other names: Asparaginase, Vincristine, Cyclophosphomide, Cytarabine, 6-MP, Methotrexate, Daunorubicin, Dexamethasone

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.

Other names: Dexamethasone, Asparaginase, Vincristine, Daunorubicin, Cyclophosphomide, Cytarabine, 6-MP, Methotrexate

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.

Other names: Dexamethasone, Asparaginase, Vincristine, Daunorubicin, Cyclophosphomide, Cytarabine, 6-MP, Methotrexate

Primary outcomes

  1. 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.

  2. 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%.

  3. 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.

  4. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Jingliao Zhang, MD

CONTACT

[email protected]

+86 22 23909196

Xiaofan Zhu, MD

CONTACT

[email protected]

+ 86 22 23909001

Sponsors and collaborators

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Other

Registry information

Official study title

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

Acronym: CCCG-TALL-2025

Important dates

Study start
2025
Primary completion
2030
Study completion
2031
First posted
Mar 4, 2025
Registry last updated
Aug 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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