Quizartinib for Acute Myeloid Leukemia

Not currently recruiting at 36 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an experimental drug called quizartinib for treating acute myeloid leukemia (AML) with a specific mutation known as FLT3-ITD. The goal is to evaluate how well quizartinib works alongside other chemotherapy drugs for those whose cancer has returned after remission or isn't responding to other treatments. Children and young adults with AML and this mutation, who are in relapse or treatment-resistant, might qualify to join. Participants will receive a combination of quizartinib and other standard chemotherapy drugs as part of the study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new 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.

Is there any evidence suggesting that quizartinib is likely to be safe for humans?

Research has shown that quizartinib is generally well tolerated when combined with other cancer treatments. Studies have found that it can be safely used with standard chemotherapy in adults with a specific type of acute myeloid leukemia (AML). In these trials, many patients experienced manageable side effects.

The most common side effects included nausea, headache, and low blood cell counts, which are typical for cancer treatments. Some reports noted more serious side effects, such as changes in heart rhythm, but these were rare and closely monitored.

As quizartinib is still under investigation, these findings require careful consideration. The drug has not yet received approval for regular use, so its safety remains under review. However, current research suggests it has a promising safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia (AML) that often include chemotherapy drugs like daunorubicin and cytarabine, quizartinib offers a new approach by specifically targeting a protein called FLT3. This protein is often mutated in AML and drives the cancer's growth. By inhibiting FLT3, quizartinib aims to stop the proliferation of cancer cells more effectively. Researchers are excited because this targeted action could lead to better outcomes for patients who have limited responses to existing treatments. Plus, the potential for quizartinib to be used in combination with other therapies could enhance its effectiveness even further.

What evidence suggests that quizartinib might be an effective treatment for acute myeloid leukemia?

Studies have shown that quizartinib can significantly improve survival rates in people with certain types of acute myeloid leukemia (AML). Quizartinib is a powerful drug that targets and blocks FLT3, a gene often altered in AML. Research indicates that adding quizartinib to standard chemotherapy extends patient survival compared to chemotherapy alone. Initial findings suggest that quizartinib might be especially effective for those with FLT3-ITD mutations, a common and aggressive form of AML. This treatment offers hope for those whose cancer has returned or isn't responding to other treatments. Participants in this trial will receive re-induction therapy that combines fludarabine and cytarabine with quizartinib. ^{2 4 6 7 8}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

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

My kidney, liver, and heart are functioning well.

I am between 1 month and 21 years old.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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 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]

Citations

1. vanflytahcp.com vanflytahcp.com/en/efficacy

Efficacy | VANFLYTA® (quizartinib) | HCP VANFLYTA provided superior overall survival vs standard chemotherapy alone. 1,4 The study demonstrated a statistically significant improvement in OS for the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41082703/

Quizartinib for Newly Diagnosed FLT3-ITD-Negative Acute ... The phase 3 QuANTUM-First trial showed that quizartinib significantly prolonged survival vs placebo when added to standard chemotherapy, ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/918/499415/Patient-Reported-Outcomes-in-Acute-Myeloid

Patient-Reported Outcomes in Acute Myeloid Leukemia ... Results: A total of 509 out of 539 patients from the trial (254 quizartinib; 255 placebo) were included for PRO analysis. Patient compliance ...

4. daiichisankyo.com daiichisankyo.com/files/news/pressrelease/pdf/202412/20241210_E.pdf

QuANTUM-Wild Phase 3 Trial of VANFLYTA® Initiated in ... AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%.1, 2 Targeted therapy with FLT3 inhibitors has ...

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01617-7

Quizartinib: a potent and selective FLT3 inhibitor for the ... Quizartinib (formerly AC220) is a novel, second-generation, highly potent, and selective type II FLT3 inhibitor.

6. vanflytahcp.com vanflytahcp.com/en/safety

Safety Profile | VANFLYTA® (quizartinib) | HCP Review the safety profile of VANFLYTA® (quizartinib) for the treatment of FLT3-ITD+ AML. See full Prescribing Info & Boxed WARNINGS.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03793478

NCT03793478 | Safety and Efficacy of Quizartinib in ... Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood. ClinicalTrials.gov ID NCT03793478.

8. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO-25-01841

Quizartinib for Newly Diagnosed FLT3-ITD–Negative Acute ... The flt3 inhibitor quizartinib is well tolerated when administered in conjunction with intensive chemotherapy in adults with newly diagnosed ...