Quizartinib + Chemotherapy for Leukemia

(QuANTUM-WILD Trial)

Recruiting at 386 trial locations

Overseen By Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must be taking: Chemotherapy

Must not be taking: All-trans retinoic acid

Disqualifiers: APL, Secondary AML, FLT3-ITD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding Quizartinib (also known as Vanflyta) to chemotherapy benefits patients with acute myeloid leukemia (AML) lacking the FLT3-ITD genetic feature. Participants will receive either Quizartinib with chemotherapy, chemotherapy with a placebo (a pill with no active drug), or Quizartinib with chemotherapy followed by a placebo. Ideal candidates are adults diagnosed with AML who have not received prior treatment, except for specific emergency interventions. The trial aims to determine if Quizartinib enhances the effectiveness of chemotherapy for these patients. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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, it mentions that treatment with all-trans retinoic acid (ATRA) must be discontinued before starting induction chemotherapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that quizartinib, when combined with chemotherapy, is generally well tolerated by adults with a specific type of acute myeloid leukemia (AML). Studies have found this combination effective for patients with FLT3-ITD-positive AML, a variant of the disease. Quizartinib has undergone extensive study and is considered a targeted treatment option for this aggressive blood cancer.

However, quizartinib remains an experimental drug and is not yet approved for regular use everywhere. Its safety continues to be researched. While the drug has shown promise and is generally considered safe, participants should understand the potential risks and discuss them with healthcare professionals before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Researchers are excited about using quizartinib in leukemia treatment because it works differently from standard chemotherapy options. While traditional treatments mainly target rapidly dividing cells, quizartinib specifically inhibits FLT3, a protein that often contributes to the growth of leukemia cells. This targeted action could potentially improve outcomes for patients with FLT3-mutated acute myeloid leukemia (AML). Furthermore, quizartinib is administered orally, making it more convenient compared to some intravenous treatments. These features collectively offer a promising new approach for tackling this aggressive form of cancer.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that adding quizartinib to chemotherapy can greatly improve outcomes for patients with acute myeloid leukemia (AML) that does not have the FLT3-ITD mutation. In this trial, participants in Arm A will receive quizartinib alongside chemotherapy, while those in Arm B will receive a placebo with chemotherapy. Studies found that patients taking quizartinib lived longer overall compared to those who only received chemotherapy. Specifically, after three years, 60.8% of patients on quizartinib were still alive, compared to 45.7% of those who took a placebo. This suggests that quizartinib could be a promising addition to chemotherapy for improving survival in this type of leukemia. These findings highlight the potential benefit of quizartinib for treating newly diagnosed AML patients without the FLT3-ITD mutation. ^{4 6 7 8 9}

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 adults aged 18 to 70 with newly diagnosed acute myeloid leukemia (AML) that lacks the FLT3-ITD mutation. Participants should be able to perform daily activities with minimal assistance (ECOG status of 0-2) and must understand and sign a consent form. They should be starting the standard '7+3' induction chemotherapy.

Inclusion Criteria

I can understand and sign the consent form for this trial.

I am currently on a '7+3' chemotherapy regimen.

I have been newly diagnosed with a type of leukemia called AML.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction and Consolidation Chemotherapy

Participants receive induction and consolidation chemotherapy with quizartinib or placebo for 14 days after chemotherapy completion

Up to 120 days

Maintenance Therapy

Participants receive quizartinib or placebo as maintenance therapy for up to 36 cycles

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 42 months

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Quizartinib

Trial Overview The study is testing whether adding Quizartinib, an experimental drug, to standard chemotherapy is more effective than adding a placebo in patients with AML who do not have the FLT3-ITD mutation.

How Is the Trial Designed?

Group I: Arm C: Quizartinib + Chemotherapy then Placebo Maintenance Experimental Treatment 3 Interventions

Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)

Group II: Arm A: Quizartinib + Chemotherapy Experimental Treatment 2 Interventions

Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive quizartinib at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)

Group III: Arm B: Placebo + Chemotherapy Placebo Group 2 Interventions

Participants will receive placebo at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

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

Published Research Related to This Trial

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 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 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 1 trial involving 19 newly diagnosed acute myeloid leukemia (AML) patients, quizartinib, a selective FLT3 inhibitor, was found to be safe and tolerable when combined with standard chemotherapy, with a maximum tolerated dose identified as 40 mg/d for 14 days.

The combination treatment showed promising efficacy, with 84% of patients responding and 74% achieving a composite complete response, indicating that quizartinib may enhance outcomes for patients with FLT3-ITD mutations in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of quizartinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Altman, JK., Foran, JM., Pratz, KW., et al.[2021]

Small molecule inhibitors (SMIs) for acute myeloid leukemia (AML) can be more tolerable than traditional chemotherapy, but they have a high potential for drug-drug interactions (DDIs) that can affect treatment success, especially since AML patients often take multiple medications.

CYP3A4 is the main enzyme that metabolizes these SMIs, and strong inhibitors or inducers of this enzyme can lead to increased toxicity or decreased efficacy, necessitating careful monitoring and possible dose adjustments for drugs like venetoclax and quizartinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-drug interactions of newly approved small molecule inhibitors for acute myeloid leukemia. Megías-Vericat, JE., Solana-Altabella, A., Ballesta-López, O., et al.[2020]

Rodent leukemia models, particularly L1210 and P388, are effective for screening drugs against human leukemias and lymphomas, with L1210 being the most successful for clinically active compounds and P388 better for antibiotics and natural products.

The study highlights the potential of the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) as a promising treatment for acute myelogenous leukemia (AML), showing oral activity and effectiveness against brain-invading leukemias, which could improve upon current treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Murine and human leukemias. Burchenal, JH.[2019]

Children with acute myelogenous leukemia (AML) show significantly higher drug resistance to most chemotherapy drugs compared to those with acute lymphoblastic leukemia (ALL), except for a few like cytarabine, mercaptopurine, and thioguanine.

Patients with relapsed AML exhibit similar sensitivity to certain drugs like cytarabine and idarubicin as initial AML patients, but those who died from refractory disease were notably more resistant to key drugs, indicating that drug resistance is a critical factor in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo drug resistance profile in childhood acute myelogenous leukemia: no drug is more effective in comparison to acute lymphoblastic leukemia. Styczynski, J., Wysocki, M., Debski, R., et al.[2019]

Olaparib enhances the effectiveness of conventional chemotherapy and DNMT inhibitors in treating acute myeloid leukemias driven by MLL fusion proteins, which are typically hard to treat.

The combination of olaparib with these treatments leads to significant reductions in cell growth and increased DNA damage, suggesting a mechanism where olaparib helps to induce cell cycle block and apoptosis in leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PARPi potentiates with current conventional therapy in MLL leukemia. Zhao, L., So, CWE.[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]

Recent advancements in leukemia treatments have led to high cure rates, such as over 90% for hairy cell leukemia with cladribine and rituximab, and 80-90% for acute promyelocytic leukemia using all-trans retinoic acid and arsenic trioxide.

Chronic lymphocytic leukemia, once considered incurable, may now be potentially curable with targeted therapies like Bruton tyrosine kinase inhibitors and venetoclax, showcasing the significant progress in leukemia treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cure of leukemia through the optimist's prism. Kantarjian, HM., Jain, N., Garcia-Manero, G., et al.[2023]

Quizartinib, a selective FLT3 inhibitor, was found to be well tolerated at a dose of 60 mg/m²/day in children with relapsed acute leukemia, showing a favorable toxicity profile during intensive chemotherapy.

The treatment resulted in significant biological activity, with complete inhibition of FLT3 phosphorylation in all patients and promising response rates, particularly in those with FLT3-ITD mutations, indicating potential for further testing in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study. Cooper, TM., Cassar, J., Eckroth, E., et al.[2022]

Amphotericin B can enhance the effectiveness of chemotherapy drugs like actinomycin D, adriamycin, and vincristine against AKR leukemia, even in cells that have developed resistance to these treatments.

While resistance to actinomycin D developed quickly in leukemia cells, resistance to vincristine and adriamycin occurred more slowly; however, amphotericin B still improved the efficacy of these drugs against resistant cells, although the enhancement decreased as resistance increased.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentiation of anticancer agent cytotoxicity against sensitive and resistant AKR leukemia by amphotericin B1. Valeriote, F., Medoff, G., Dieckman, J.[2015]

The combination of paclitaxel and quizartinib significantly reduces the proliferation of the MV4-11 leukemia cell line and increases apoptosis compared to either drug alone, indicating a synergistic effect.

This combination therapy works by inhibiting the FLT3/STAT5 signaling pathway, as evidenced by lower levels of phosphorylated FLT3 and STAT5 proteins in the combination group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of Paclitaxel and Quizartinib Alone and in Combination on AML Cell Line MV4-11 and Its STAT5 Signal Pathway]. Bai, ZW., Wu, MQ., Zhou, BW., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-01841

Quizartinib for Newly Diagnosed FLT3-ITD–Negative Acute ... Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively (P=0.012); three-year OS rates were 60.8% and 45.7%.

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

Quizartinib for Newly Diagnosed FLT3-ITD-Negative Acute ... Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively (P=0.012); three-year OS rates were 60.8% and 45.7%.

3. 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 ...

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

QuANTUM-Wild Phase 3 Trial of VANFLYTA® Initiated in ... “Preliminary data have shown promising results for VANFLYTA in patients with FLT3-ITD negative acute myeloid leukemia, which includes ...

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

Patient-Reported Outcomes in Acute Myeloid Leukemia ... Quizartinib demonstrated a clinically meaningful and statistically significant improvement in overall survival (OS) versus placebo. An ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03793478

NCT03793478 | Safety and Efficacy of Quizartinib in ... 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37116523/

Quizartinib plus chemotherapy in newly diagnosed patients ... Quizartinib provides a new, effective, and generally well tolerated treatment option for adult patients with FLT3-ITD-positive newly diagnosed AML.

8. 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.

9. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/cpdd.1353

Safety and Pharmacokinetics of Quizartinib Combination ... It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients with FLT3-internal tandem ...