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Active, not recruitingNCT04233346Updated Apr 4, 2025

The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs or With T315I Mutation

A Phase 2 interventional study of Ponatinib 30mg OD and Ponatinib 45mg OD in Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia, sponsored by Otsuka Beijing Research Institute. Active, not recruiting at 14 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-04.

Sponsored by Otsuka Beijing Research Institute · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
93
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This protocol will allow ponatinib with refractory Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia

Read the detailed description

The purpose of this study is to determine the safety and efficacy of ponatinib in patients with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with Ph positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the T315I mutation.

02

Conditions studied

  • Chronic Myeloid Leukemia
  • Acute Lymphoblastic Leukemia

Keywords

  • Acute Lymphoblastic Leukemia
  • Chronic Myeloid Leukemia
  • ponatinib
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 93 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Otsuka Beijing Research Institute is the lead sponsor of 36 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

For CP-CML patients:

  1. Patients with CP-CML

    Patients must either meet criterion 2 or 3:

  2. Be previously treated with and resistant or intolerant to either Dasatinib or Nilotinib:
  3. Develop the T315I mutation after any TKI therapy;
  4. Must be ≥18 years old.
  5. Provide written informed consent.
  6. Eastern Cooperative Oncology Group performance status ≤ 2.
  7. Minimum life expectancy of 3 months or more.
  8. Adequate renal function
  9. Adequate hepatic function
  10. Normal pancreatic status
  11. Normal QTc interval on screening electrocardiogram (ECG) evaluation under resting state, defined as QTc of ≤ 450 ms in males or ≤ 470 ms in females.

For AP/BP-CML and ALL patients:

  1. Patients with AP-CML and BP-CML or Ph+ ALL
  2. Other inclusions are the same with No.2-No.11 of CP-CML patients

Exclusion criteria

Exclusion Criteria:

For CP-CML patients:

  1. Received TKI therapy within 7 days prior to receiving the first dose of Ponatinib, or have not recovered (> grade 2 by NCI CTCAE v5.0) from AEs (except alopecia) due to agents previously administered.
  2. Received other therapies (excluding hydroxyurea) as follows:

    Received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of Ponatinib.

  3. Underwent autologous or allogeneic stem cell transplant \< 60 days prior to receiving the first dose of Ponatinib;
  4. Take medications that are known to be associated with Torsades de Pointes or QT interval prolongation.
  5. Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
  6. Have previously been treated with Ponatinib or its analogues (including drug substance).
  7. Patients with CP-CML are excluded if they are in CCyR.
  8. Have active central nervous system (CNS) disease, as evidenced by cytology or pathology.
  9. Have significant, uncontrolled, or active heart/brain/peripheral vascular diseases
  10. Have a significant bleeding disorder unrelated to CML
  11. Have a history of pancreatitis or alcohol abuse
  12. Severely increased hypertriglyceridemia (triglycerides ≥ 5.6 mmol/L).
  13. Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered Ponatinib.
  14. Have been diagnosed with another primary malignancy within the past 3 years (except for non-melanoma skin cancer, cervical cancer in situ, or controlled prostate cancer, which are allowed within 3 years).
  15. Are pregnant or lactating.
  16. Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days prior to first dose of Ponatinib.
  17. Infectious diseases test showed anti-HIV (+) or anti-HCV (+) or HbsAg (+) or TP (+).
  18. Suffer from any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the safety of the study drug.
  19. Have hypertension (diastolic blood pressure ≥ 90 mmHg and/or systolic blood pressure ≥ 140 mm Hg).
  20. Taken herbal preparations or related over-the-counter preparations containing Chinese herbal ingredients within 2 weeks prior to the first dose of Ponatinib.
  21. Any subject who is not suitable for the study in the opinion of the investigator.

For AP/BP-CML and ALL patients:

  1. Received TKI therapy within 7 days prior to receiving the first dose of Ponatinib, or have not recovered (> grade 2 by NCI CTCAE v.5.0) from AEs (except alopecia) due to agents previously administered.
  2. Received other therapies (excluding hydroxyurea) as follows:

    For AP-CML patients, received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of Ponatinib.

    For BP-CML patients, received chemotherapy within 7 days prior to the first dose of Ponatinib. Otherwise, 2a applies.

    For Ph+ ALL patients, received corticosteroids within 24 hours before the first dose of Ponatinib; otherwise, 2a applies.

  3. Underwent autologous or allogeneic stem cell transplant \< 60 days prior to receiving the first dose of Ponatinib.
  4. Take medications that are known to be associated with Torsades de Pointes or QT interval prolongation.
  5. Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
  6. Have previously been treated with Ponatinib or its analogues (including drug substance).
  7. Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if they are in MaHR.
  8. Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if a baseline BM aspirate adequate for cell count and differential report is not available.
  9. Have active central nervous system (CNS) disease as evidenced by cytology or pathology for AP-CML, BP-CML, or Ph+ ALL.
  10. Have significant, uncontrolled, or active cardiovascular disease.
  11. Have a significant bleeding disorder unrelated to CML or Ph+ ALL.
  12. Other exclusions are the same with No.11-No.21 of CP-CML.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
93 participants (actual)

Study arms

  • Experimental
    Ponatinib 30mg

    50% CML patients will be treated with 30mg/day ponatinib,the treatment will up to 60 months

    Drug: Ponatinib 30mg OD

  • Experimental
    Ponatinib 45mg

    50% CP-CML patients will be randomized 45 mg dose group . Other patients (with AP-CML, BP-CML, Ph+ ALL) will only be assigned to 45 mg dose group(30 patients). The treatment will up to 60 months.

    Drug: Ponatinib 45mg OD

Interventions

  • DrugPonatinib 30mg OD

    Ponatinib 30mg OD

  • DrugPonatinib 45mg OD

    Ponatinib 45mg OD

06

What researchers measure

Primary outcomes

  1. MCyR(Major Cytogenetic Response) of CP-CML patients

    To confirm the efficacy of Ponatinib in Chinese patients with CML who have failed Dasatinib or Nilotinib or with T315I mutation, or Ph+ ALL who have failed prior TKIs or with T315I mutation as evidenced by cytogenetic responses

    Time frame: 12 months

  2. MaHR(Major Hematologic Response) of AP-CML, BP-CML and Ph+ ALL patients by 6 months

    To confirm the efficacy of Ponatinib in Chinese patients with CML who have failed Dasatinib or Nilotinib or with T315I mutation, or Ph+ ALL who have failed prior TKIs or with T315I mutation as evidenced by hematology responses

    Time frame: 6 months

Secondary outcomes

  1. Duration of response

    Assessment in the total patient population

    Time frame: Up to 5 years

  2. Progression-free survival (PFS)

    Assessment in the total patient population

    Time frame: Up to 5 years

  3. Overall survival (OS)

    Assessment in the total patient population

    Time frame: Up to 5 years

  4. Time to response (TTR)

    Assessment in the total patient population

    Time frame: Up to 5 years

  5. Adverse events

    Number of participants with adverse events as assessed by CTCAE v5.0

    Time frame: Up to 5 years

  6. EORTC QLQ-C30 (version 3)

    EORTC QLQ-C30 (version 3) score ranges from 1 to 4 or 1 to 7, A higher score represents a severer impressions or a best applies of patients.

    Time frame: Up to 5 years

  7. Maximum Plasma Concentration [Cmax]

    Plasma concentration-time data for the population PK study

    Time frame: Up to 3 months

07

Study locations

14 sites
  • Anhui Provincial Hospital
    Hefei, Anhui, China
  • The First Affiliated Hospital of Anhui Medical University
    Hefei, Anhui, China
  • Nanfang Hospital of Southern Medical University
    Guangzhou, Guangdong, China
  • Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
    Wuhan, Hubei, China
  • Xiangya Hospital Central South University
    Changsha, Hunan, China
  • The First Affiliated Hospital of Soochow University
    Suzhou, Jiangsu, China
  • Shengjing Hospital of China Medical University
    Shenyang, Liaoning, China
  • Qilu Hospital of Shandong University
    Jinan, Shandong, China
  • Second hospital of Shanxi Medical University
    Taiyuan, Shanxi, China
  • Shenzhen Second People's Hospital
    Shenzhen, Shenzhen, China
  • West China Hospital, Sichuan University
    Chengdu, Sichuan, China
  • The First Affiliated Hospital of Medical School of Zhejiang University
    Hangzhou, Zhejiang, China
  • 1st affiliated hospital, Peking University
    Beijing, China
  • Hematology Hospital, Chinese Academy of Medical Sciences
    Tianjin, China
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 4, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04233346
Lead sponsor
Otsuka Beijing Research Institute
Responsible party
Sponsor
First posted
Jan 18, 2020
Start date
Jul 9, 2020
Primary completion
Jul 22, 2022
Completion
Dec 31, 2025 (estimated)
Last update
Apr 4, 2025

Study contacts

Juma Paty, Director
study director · OBRI

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.

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