Olverembatinib for Chronic Myelogenous Leukemia

Overseen By Fadi Haddad, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Cardiac disease, Bleeding disorders, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if olverembatinib can help to control newly diagnosed CML in the chronic phase.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on an FDA-approved TKI, you must not have taken it for more than 30 days to be eligible.

What data supports the effectiveness of the drug Olverembatinib for treating chronic myelogenous leukemia?

The research highlights that similar drugs, like imatinib, nilotinib, and dasatinib, have significantly improved outcomes and quality of life for patients with chronic myelogenous leukemia by targeting the BCR-ABL protein, which is involved in the disease. This suggests that Olverembatinib, if it works similarly, could also be effective. ^{1 2 3 4 5}

Is Olverembatinib safe for humans?

Olverembatinib has been studied in patients with chronic myeloid leukemia and appears to be a safe treatment option, with research showing it is well-tolerated in patients with certain mutations. ^{6 7 8 9 10}

Research Team

Fadi Haddad, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults (≥18 years) with newly diagnosed chronic myeloid leukemia in the chronic phase can join. They must be willing to use birth control and have not had extensive prior treatments for CML. Participants need to have good organ function, no severe heart issues or psychiatric disorders, and cannot be pregnant.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and 4 months after completion of olverembatinib administration

Approved methods of birth control include hormonal contraception, intrauterine device (IUD), tubal ligation or hysterectomy, participant post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to olverembatinib or other agents used in study

Participants with active, uncontrolled psychiatric disorders including psychosis, major depression, and bipolar disorders

Participants who are receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olverembatinib monotherapy at a dose of 30 mg orally every other day

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Olverembatinib

Trial Overview The trial is testing olverembatinib as a single therapy to see if it controls chronic myeloid leukemia in its early stage. It's for patients who haven't received much previous treatment and are now trying this medication for the first time.

Participant Groups

Group I: Treatment with Olveremebatinib Experimental Treatment 1 Intervention

Patients will receive single agent olverembatinib at a dose of 30 mg orally every other day (QOD)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Ascentage Pharma Group Inc.

Industry Sponsor

Trials

54

Recruited

5,700+

Findings from Research

In a cost-effectiveness analysis involving 100 patients with chronic myeloid leukemia, nilotinib was found to provide more progression-free life-years saved (15.21) compared to imatinib (12.64) and dasatinib (14.91), indicating its superior efficacy as a first-line treatment.

Nilotinib was also shown to be more cost-effective than dasatinib, with a lower incremental cost-effectiveness ratio of US$ 33,120.36 per progression-free life-year saved, making it the preferred option for treatment in Colombia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of nilotinib, dasatinib and imatinib as first-line treatment for chronic myeloid leukemia in Colombia, 2012. Romero, M., Chávez, D., De Los Ríos, M., et al.[2022]

Imatinib, a targeted inhibitor of the BCR-ABL fusion protein, has significantly improved survival rates for patients with chronic myelogenous leukemia (CML), but some patients develop resistance or intolerance to this therapy.

Second-generation tyrosine kinase inhibitors like nilotinib and dasatinib, along with newer options like ponatinib and bosutinib, provide additional treatment choices for CML, enhancing patient outcomes and quality of life, and ongoing clinical trials are exploring the best ways to use these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy in chronic myelogenous leukemia: where do emerging therapies fit within current treatment regimens? Mauro, MJ., Talpaz, M., Radich, JP.[2017]

In a long-term study with a median follow-up of 10.9 years, imatinib demonstrated a high overall survival rate of 83.3% in patients with chronic myeloid leukemia (CML), indicating its sustained efficacy as an initial treatment.

Serious adverse events related to imatinib were rare and mostly occurred within the first year of treatment, suggesting that long-term use of imatinib is safe and does not lead to unacceptable cumulative toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. Hochhaus, A., Larson, RA., Guilhot, F., et al.[2022]

Olverembatinib (HQP1351) is a third-generation tyrosine kinase inhibitor specifically designed to target BCR-ABL1 mutations, including the T315I mutation that causes resistance to earlier treatments, making it a promising option for patients with chronic myeloid leukaemia (CML).

In November 2021, olverembatinib was approved in China for adult patients with TKI-resistant chronic-phase or accelerated-phase CML harboring the T315I mutation, indicating its efficacy in overcoming resistance that limits other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib: First Approval. Dhillon, S.[2022]

Olverembatinib is a novel oral tyrosine kinase inhibitor that effectively targets the T315I mutation in the BCR::ABL1 tyrosine kinase, which is a significant cause of resistance in chronic myeloid leukemia (CML) treatment.

Recent studies suggest that olverembatinib is a safe and effective treatment option for CML patients with the T315I mutation, addressing a critical challenge in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib in chronic myeloid leukemia. Öziskender, R., Eşkazan, AE.[2022]

In a study of 450 patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs) from 2004 to 2014, the 5-year overall survival rate was 95.1%, indicating high efficacy of TKIs in this patient population.

Severe adverse events (AEs) during first-line TKI therapy were linked to lower overall survival and event-free survival rates, suggesting that timely modifications to treatment are crucial when patients experience significant AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia. Ota, S., Matsukawa, T., Yamamoto, S., et al.[2022]

Olverembatinib demonstrated significant antileukemic activity in adults with TKI-resistant chronic myeloid leukemia (CML), particularly in patients with the T315I mutation, with 3-year cumulative incidences of major cytogenetic response (MCyR) reaching 79% in chronic phase (CML-CP) and 47.4% in accelerated phase (CML-AP).

The treatment was well tolerated, with common side effects including skin hyperpigmentation and severe thrombocytopenia, indicating a manageable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial. Jiang, Q., Li, Z., Qin, Y., et al.[2023]

In a study of 81 patients with chronic myeloid leukemia (CML) treated with imatinib over two years, 326 adverse drug reactions (ADRs) were reported, with hematological toxicities being the most common, particularly thrombocytopenia at 21.17%.

Most ADRs were classified as mild to moderate, indicating that while imatinib can cause significant side effects, they are generally manageable, highlighting the need for careful monitoring to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study. Francis, J., Palaniappan, M., Dubashi, B., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment options for patients with chronic myeloid leukemia who are resistant to or unable to tolerate imatinib. [2022]

2. Colombia pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of nilotinib, dasatinib and imatinib as first-line treatment for chronic myeloid leukemia in Colombia, 2012. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Comparing nilotinib with dasatinib as second-line therapies in patients with chronic myelogenous leukemia resistant or intolerant to imatinib -- a retrospective chart review analysis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Sequential therapy in chronic myelogenous leukemia: where do emerging therapies fit within current treatment regimens? [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Olverembatinib: First Approval. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Olverembatinib in chronic myeloid leukemia. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial. [2023]

10. India pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study. [2020]