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

NCT04233346 | Active Not Recruiting Phase 2

• 1 other identifier: 297-403-00003
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 14

Brief Summary

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

Conditions

Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic Leukemia; Chronic Myeloid Leukemia; ponatinib

Outcome Measures

Primary Outcomes (2)

• 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

  12 months

• 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

  6 months

Secondary Outcomes (7)

• Duration of response

  Up to 5 years

• Progression-free survival (PFS)

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

• Time to response (TTR)

  Up to 5 years

• Adverse events

  Up to 5 years

Study Arms (2)

Ponatinib 30mg

EXPERIMENTAL

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

Drug: Ponatinib 30mg OD

Ponatinib 45mg

EXPERIMENTAL

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

Ponatinib 30mg OD DRUG

Ponatinib 30mg OD

Ponatinib 30mg

Ponatinib 45mg OD DRUG

Ponatinib 45mg OD

Ponatinib 45mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For CP-CML patients：
• Patients with CP-CML
• Patients must either meet criterion 2 or 3:
• Be previously treated with and resistant or intolerant to either Dasatinib or Nilotinib:
• Develop the T315I mutation after any TKI therapy;
• Must be ≥18 years old.
• Provide written informed consent.
• Eastern Cooperative Oncology Group performance status ≤ 2.
• Minimum life expectancy of 3 months or more.
• Adequate renal function
• Adequate hepatic function
• Normal pancreatic status
• 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：
• Patients with AP-CML and BP-CML or Ph+ ALL

You may not qualify if:

• For CP-CML patients：
• 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.
• 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.
• Underwent autologous or allogeneic stem cell transplant \< 60 days prior to receiving the first dose of Ponatinib;
• Take medications that are known to be associated with Torsades de Pointes or QT interval prolongation.
• Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
• Have previously been treated with Ponatinib or its analogues (including drug substance).
• Patients with CP-CML are excluded if they are in CCyR.
• Have active central nervous system (CNS) disease, as evidenced by cytology or pathology.
• Have significant, uncontrolled, or active heart/brain/peripheral vascular diseases
• Have a significant bleeding disorder unrelated to CML
• Have a history of pancreatitis or alcohol abuse
• Severely increased hypertriglyceridemia (triglycerides ≥ 5.6 mmol/L).
• Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered Ponatinib.

Sponsors & Collaborators

• Otsuka Beijing Research Institute: lead

Study Sites (14)

Anhui Provincial Hospital

Hefei, Anhui, China

Location

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

Location

Qilu Hospital of Shandong University

Jinan, Shandong, China

Location

Second hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Location

Shenzhen Second People's Hospital

Shenzhen, Shenzhen, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

The First Affiliated Hospital of Medical School of Zhejiang University

Hangzhou, Zhejiang, China

Location

1st affiliated hospital, Peking University

Beijing, China

Location

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, China

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Juma Paty, Director

  OBRI

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2019
• First Posted: January 18, 2020
• Study Start: July 9, 2020
• Primary Completion: July 22, 2022
• Study Completion: December 31, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (14)