HQP1351CU101 = Study of HQP1351 in subjects with refractory chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia [USA]

What is the purpose of the study

This is a phase 1b study to evaluate the pharmacokinetics of HQP1351 and to determine the recommended dose for phase 2 in subjects with CML chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with Ph+ ALL, who have developed resistance or intolerance to at least two prior tyrosin kinase inhibitors (TKIs) or in subjects with Ph+ B-cell precursor (BCP) ALL or lymphoid blast phase CML (LBP), who have experienced resistance or intolerance to at least one second or later generation TKI. The preliminary efficacy and safety of HQP1351 in these patients will be evaluated as well.

What will happen during the study

In this study, patients with CML in chronic phase, accelerated phase, or blast phase will receive HQP1351 at a dose of either 30 mg, 40 mg, or 50 mg by mouth every other day for 28 days. (Cohort A, B, and C)

Patients with CML in lymphoid blast phase will receive HQP1351 at an initial dose of 30 mg by mouth every other day with blinatumomab as a continuous intravenous infusion at repeated 42-day cycles. (Cohort D)

Key inclusion criteria

This study includes male or female patients who:

• are 18 years or older.
• have been diagnosed with with CML in chronic phase or accelerated phase or blast phase or with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL), with or without T315I mutation.
• for Cohort A, B, and C: have been previously treated with and developed resistance or intolerance to at least two TKIs, including ponatinib, imatinib, dasatinib, nilotinib, bosutinib, and asciminib. For patients with a T315I mutation, the number of previously given TKIs is not restricted.
• for Cohort D: have been diagnosed with with Ph+ BCP ALL or CML LBP and are resistant or intolerant to at least one second or later generation TKI, such as dasatinib, nilotinib, bosutinib and ponatinib, despite optimal supportive care.
• have adequate end-organ function.
• have an Eastern Co-Operative Oncology Group (ECOG) status of 0, 1 or 2.

Further criteria may apply. Please discuss these with your doctor or study staff.

Key exclusion criteria

This study does not include patients who:

• have received TKI therapy within 5 half-lives or 7 days prior to the first dose of HQP1351, whichever is shorter,
• have experienced adverse events (except alopecia [hair loss] and pigmentation) ndue to any other treatments and have not recovered.
• have received other therapies as follows:
  1. For CP and AP patients, received hydroxyurea or anagrelide within 24 hours prior to the first dose of HQP1351; or, interferon, immunotherapy or cytarabine within 14 days prior to the first dose of HQP1351; or, any other radiotherapy, cytotoxic chemotherapy or investigational therapy within 28 days prior to receiving the first dose of HQP1351
  2. For BP patients, received chemotherapy within 7 days prior to the first dose of HQP1351
  3. For Ph+ ALL patients, received corticosteroids within 24 hours before the first dose of HQP1351, or received chemotherapy within 7 days prior to the first dose of HQP1351
  4. Patients who are currently receiving treatment with a medication that has the potential to interact with HQP1351
  5. Patients who had been treated with HQP1351
  6. Patients requiring immunosuppressive therapy other than short time of steroid.

Further criteria may apply. Please discuss these with your doctor or study staff.

Estimated primary completion date

Where can I find additional information

You can find a study description in the US register ClinicalTrials.gov. This is a database provided by the U. S. National Institutes of Health.

Study centers / principal investigators

United States

Alabama

University of Alabama at Birmingham
Birmingham, Alabama, 35294
Principal Investigator: Omer Jamy, MD

Arkansas

Highlands Oncology
Rogers, Arkansas, 72758
Principal Investigator: Thad Beck, MD

California

City of Hope
Duarte, California, 91010
Principal Investigator: Paul Koller, MD

Georgia

Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Principal Investigator: Anthony Hunter, MD

Maryland

University of Maryland
Baltimore, Maryland, 21201
Principal Investigator: Maria Baer, MD

Ohio

Cleveland Clinic
Cleveland, Ohio, 44195
Principal Investigator: Sudipto Mukherjee, MD

Texas

University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Contact: Elias Jabbour, MD

Washington

Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Principal Investigator: Vivian Oehler, MD