Quizartinib for Acute Myeloid Leukemia

Recruiting at 32 trial locations

Overseen By Daiichi Sankyo Contact for Clinical Information

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Daiichi Sankyo

Must not be taking: Chemotherapy, Radiation, Immunotherapy, others

Disqualifiers: CNS relapse, APL, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

65 Participants Needed

Trial Summary

What is the purpose of this trial?

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research. Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to join this study if it has come back after remission or is not responding to treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot receive other chemotherapy, radiation, or immunotherapy during the study unless specified in the protocol.

What data supports the effectiveness of the drug Quizartinib for treating Acute Myeloid Leukemia?

Research shows that Quizartinib, a drug targeting a specific mutation in leukemia cells, improved survival in patients with a certain type of Acute Myeloid Leukemia (AML) compared to standard chemotherapy. In one study, patients with the FLT3-ITD mutation who received Quizartinib lived longer and had better response rates than those who did not receive the drug. ^{1 2 3 4 5}

Is Quizartinib safe for humans?

Quizartinib has been tested in several clinical trials for acute myeloid leukemia, showing some side effects like low blood cell counts and stomach bleeding, but it was generally tolerated by most participants. More studies are needed to fully understand its safety, especially when used with other treatments. ^{2 6 7 8 9}

What makes the drug Quizartinib unique for treating acute myeloid leukemia?

Quizartinib is unique because it is an oral drug that specifically targets and inhibits the FLT3 gene mutation, which is common in acute myeloid leukemia and associated with poor outcomes. This targeted approach can lead to better survival rates compared to traditional chemotherapy, especially in patients with the FLT3-ITD mutation. ^{2 3 4 6 7}

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

This trial is for children and young adults aged 1 month to 21 years with a specific blood cancer (FLT3-ITD AML) that's returned or isn't responding to treatment. They must have tried no more than one remission induction, be in good health otherwise, and agree to use effective birth control.

Inclusion Criteria

I am between 1 month and 21 years old.

My kidney, liver, and heart are functioning well.

If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later

Exclusion Criteria

I do not have active hepatitis B or C.

Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)

I have a known history of HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation/De-escalation

Participants are enrolled by dose-level to determine the recommended Phase 2 dose (RP2D) of quizartinib for pediatric participants.

Varies by participant

Dose Expansion

Participants receive the RP2D of quizartinib for their respective age group.

Varies by participant

Re-Induction Therapy

Participants receive fludarabine/cytarabine followed by quizartinib as a single agent, with intrathecal chemotherapy prophylaxis.

56 days

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Period

Participants are evaluated for eligibility to undergo HSCT. If not immediately available, they may receive a 28-day cycle of consolidation therapy.

28 days

Continuation Therapy

Participants in remission after HSCT, or who achieve at least a partial remission, receive up to 12 cycles of quizartinib continuation therapy.

12 months

Long-term Follow-up

Participants are monitored for survival and anti-leukemic treatments every 3 months for the first 2 years, then annually.

3 years

Treatment Details

Interventions

• Quizartinib

Trial Overview The study tests Quizartinib, an experimental drug not yet approved for regular use, alongside other chemotherapy drugs like Fludarabine and Cytarabine. It targets patients whose leukemia has relapsed or is resistant to initial treatments.

Participant Groups

Group I: All Participants Experimental Treatment 5 Interventions

All participants will receive re-induction therapy that includes fludarabine and cytarabine in combination with experimental drug quizartinib. For prophylaxis, IT chemotherapy with cytarabine, methotrexate and prednisolone/hydrocortisone will be given prior to or between re-induction cycles. After completing re-induction therapy, eligible participants may also receive optional consolidation chemotherapy which includes cytarabine, etoposide and quizartinib, if HSCT is not available immediately. After completing re-induction or HSCT successfully, eligible participants can go on to receive continuation therapy with quizartinib.

Quizartinib is already approved in United States, Japan for the following indications:

Approved in United States as Vanflyta for:

• Acute myeloid leukemia (AML)

Approved in Japan as Vanflyta for:

• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Lead Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Innovative Therapies For Children with Cancer Consortium

Collaborator

Trials

14

Recruited

2,100+

Findings from Research

In a study of 202 older patients with acute myeloid leukemia (AML) who were not suitable for intensive chemotherapy, the addition of quizartinib to low-dose ara-C (LDAC) did not improve overall survival for the entire group, but it significantly enhanced response rates in patients with the FLT3-ITD mutation.

For the 27 FLT3-ITD patients, those receiving quizartinib plus LDAC had a median overall survival of 13.7 months compared to 4.2 months for those on LDAC alone, indicating that quizartinib could be a promising option for improving outcomes in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Dennis, M., Thomas, IF., Ariti, C., et al.[2022]

Quizartinib, a selective FLT3 inhibitor, demonstrated significant efficacy in treating relapsed or refractory acute myeloid leukaemia, particularly in patients with FLT3-ITD mutations, with 56% of FLT3-ITD-positive patients in cohort 1 achieving composite complete remission.

The treatment was generally well tolerated, although serious adverse events occurred in a notable percentage of patients, including febrile neutropenia and QTc prolongation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Cortes, J., Perl, AE., Döhner, H., et al.[2023]

In a phase III trial, the FLT3 inhibitor quizartinib showed a survival benefit compared to traditional chemotherapy in patients with relapsed or refractory FLT3-mutant acute myeloid leukemia.

The promising results from quizartinib suggest it may become a first-line treatment option for this type of leukemia, pending outcomes from ongoing studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib Bests Chemo for FLT3-Mutant AML. [2019]

In a phase 3 trial involving 367 patients with relapsed or refractory FLT3-ITD-positive acute myeloid leukaemia, treatment with quizartinib resulted in a longer median overall survival of 6.2 months compared to 4.7 months for those receiving standard chemotherapy, indicating a significant survival benefit.

Quizartinib demonstrated a manageable safety profile, with common serious adverse events being similar to those seen in chemotherapy, suggesting it could be a new standard of care for patients with this aggressive form of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Cortes, JE., Khaled, S., Martinelli, G., et al.[2020]

In a study involving 93 healthy subjects, quizartinib showed a significant increase in plasma concentration when coadministered with the strong CYP3A inhibitor ketoconazole, indicating that dose adjustments may be necessary to avoid potential toxicity.

The study found that quizartinib had a low incidence of related adverse events (5.4%), with no serious adverse events or deaths reported, suggesting it is generally safe when administered alone or with moderate CYP3A inhibitors like fluconazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite. Li, J., Kankam, M., Trone, D., et al.[2021]

Quizartinib is an effective treatment for patients with FLT3-ITD acute myeloid leukemia (AML), as it inhibits the FLT3 gene activity, leading to tumor cell death, and has shown promise in clinical trials for relapsed or refractory cases.

The drug has received breakthrough therapy designation from the FDA, highlighting its potential, but further studies are necessary to assess its safety, efficacy in combination with other treatments, and to address its side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib (AC220): a promising option for acute myeloid leukemia. Zhou, F., Ge, Z., Chen, B.[2020]

In a phase 1 study involving 13 patients with FLT3-ITD-mutated acute myeloid leukemia (AML) after allogeneic hematopoietic-cell transplant, quizartinib showed acceptable tolerability as a maintenance therapy, with 77% of subjects receiving it for over a year.

The study indicated early evidence of reduced relapse rates with quizartinib maintenance therapy, although some patients experienced significant adverse events, including neutropenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 1 study of quizartinib as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic stem cell transplant. Sandmaier, BM., Khaled, S., Oran, B., et al.[2023]

References

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

Randomized evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. [2023]

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

Quizartinib Bests Chemo for FLT3-Mutant AML. [2019]

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

Transient exposure to quizartinib mediates sustained inhibition of FLT3 signaling while specifically inducing apoptosis in FLT3-activated leukemia cells. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Effects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite. [2021]

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

Quizartinib (AC220): a promising option for acute myeloid leukemia. [2020]

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

Population Pharmacokinetic Analysis of Quizartinib in Healthy Volunteers and Patients With Relapsed/Refractory Acute Myeloid Leukemia. [2021]

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

Results of a phase 1 study of quizartinib as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic stem cell transplant. [2023]