TAS1440 + ATRA for Leukemia

No longer recruiting at 16 trial locations

Overseen By General Inquiries

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Taiho Oncology, Inc.

Must not be taking: Calcineurin inhibitors, Retinoids

Disqualifiers: CNS leukemia, BCR-ABL leukemia, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called TAS1440 for people with acute myeloid leukemia (AML) that hasn't responded to other treatments or has returned. Initially, the study examines TAS1440 alone, followed by its combination with ATRA (All-trans retinoic acid, a form of vitamin A used in cancer treatment). The goal is to determine if these treatments can control the cancer and improve symptoms. Individuals with AML that has returned or not improved after previous treatments might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how TAS1440 works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational therapy, you must stop it at least 2 weeks before starting the study treatment.

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

Research has shown that TAS1440, used alone or with all-trans retinoic acid (ATRA), is safe with manageable side effects. In past studies with similar drug combinations, patients experienced side effects that were neither severe nor harmful. This current study is in its early stages, focusing primarily on assessing the treatment's safety for people. While promising evidence suggests that TAS1440 and ATRA are safe, researchers are gathering more information to confirm these early results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for leukemia, which often include chemotherapy and targeted therapies, TAS1440 offers something new. Researchers are excited about TAS1440 because it works by inhibiting a specific protein that is crucial for cancer cell survival, potentially making it more effective at stopping leukemia cells in their tracks. Additionally, when combined with ATRA, a compound that promotes the differentiation of cancer cells, this treatment could enhance the overall effect, offering a more potent option against the disease. This novel approach might lead to better outcomes for patients who have limited options with existing therapies.

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

Research has shown that TAS1440, which participants in this trial may receive, may be effective against leukemia, particularly in patients with certain genetic changes known as FLT3 ITD mutations. In early animal studies, TAS1440 significantly reduced tumor growth. This trial also tests TAS1440 in combination with another treatment called all-trans retinoic acid (ATRA). ATRA has successfully treated a different type of leukemia by helping cancer cells mature and stop growing. These treatments are tested together in one arm of the trial to determine if they can help treat acute myeloid leukemia (AML) that has returned or hasn't responded to previous treatments. ^{3 5 6 7 8}

Who Is on the Research Team?

James Lowder, MD

Principal Investigator

Astex Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with acute myeloid leukemia (AML) who have not responded to standard treatments or whose disease has returned. They should be in a condition stable enough to complete at least one treatment cycle, have an acceptable level of organ function, and women must not be pregnant or breastfeeding. People with certain heart conditions, active infections, other cancers needing treatment, or those unable to take oral medication cannot join.

Inclusion Criteria

- AST and ALT <5 × ULN (if considered due to leukemic organ involvement).

I have a diagnosed condition.

My kidney function is within the normal range.

Exclusion Criteria

My bilirubin levels are high, or I have severe liver disease.

I am not undergoing active treatment for a second cancer, except if it's breast or prostate cancer being managed with hormone therapy.

I have been diagnosed with a specific type of leukemia called acute promyelocytic leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

TAS1440 administered as a single agent once daily on specific days during each 28-day cycle

28-day cycles

Treatment Part 2

TAS1440 administered once daily on specific days in combination with ATRA twice daily during each 28-day cycle

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ATRA
• TAS1440

Trial Overview The study is testing TAS1440 alone and combined with ATRA in people with relapsed/refractory AML. It aims to evaluate the safety and effectiveness of these treatments over approximately 30 months. Participants will receive TAS1440 as a single agent first then in combination with ATRA.

How Is the Trial Designed?

Group I: TAS1440 + ATRA Experimental Treatment 1 Intervention

TAS1440 administered QD on specific days during each 28-day cycle in combination with ATRA twice daily (BID) in Part 2.

Group II: TAS1440 Experimental Treatment 1 Intervention

TAS1440 as a single agent administered once daily (QD) on specific days during each 28-day cycle in Part 1.

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Astex Pharmaceuticals, Inc.

Lead Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

Published Research Related to This Trial

Tandutinib, a FLT3 inhibitor, shows promising antileukemic activity in about half of AML patients, especially those with FLT3 ITD mutations, and does not cause common chemotherapy side effects like myelosuppression or cardiac toxicity.

Combining tandutinib with standard chemotherapy (the '3 + 7' regimen) enhances its effectiveness and may allow for lower doses of chemotherapy, reducing side effects, making it a potentially safer option for elderly or medically compromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FLT3 inhibitor tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin. Schittenhelm, MM., Kampa, KM., Yee, KW., et al.[2020]

In a study involving 7 patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts, PR-104 demonstrated significantly greater efficacy against T-lineage ALL (T-ALL) compared to B-cell-precursor ALL (BCP-ALL), suggesting it may be a promising treatment for T-ALL.

The expression of the enzyme AKR1C3 was found to be a predictive biomarker for PR-104 sensitivity, as higher levels of AKR1C3 in T-ALL xenografts correlated with increased sensitivity to the drug, indicating that testing for AKR1C3 could help identify patients who would benefit most from PR-104 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia. Moradi Manesh, D., El-Hoss, J., Evans, K., et al.[2021]

In a phase I trial involving 37 pediatric patients with relapsed/refractory acute myeloid leukemia (R/R AML), the combination of decitabine, vorinostat, and FLAG chemotherapy showed a promising overall response rate of 54%, with 16 patients achieving complete response (CR).

The treatment was well-tolerated with no dose-limiting toxicities, and among those who responded, 90% achieved minimal residual disease (MRD) negativity, leading to a significantly higher two-year overall survival rate of 75.6% for MRD-negative patients compared to 17.9% for those with residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium. Pommert, L., Schafer, ES., Malvar, J., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-2-2020-813fd

TAS1440 + ATRA for Leukemia · Info for Participants Tandutinib, a FLT3 inhibitor, shows promising antileukemic activity in about half of AML patients, especially those with FLT3 ITD mutations, and does not cause ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04282668

A Study of TAS1440 With ATRA in Subjects With r/r AML This is a multicenter, 2-part, Phase 1 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of TAS1440 ...

3. bioworld.com bioworld.com/articles/691081-preclinical-studies-support-use-of-tas-1440-in-combination-with-anti-pd-1-antibodies-for-treatment-of-immunotherapy-resistant-cancer

Preclinical studies support use of TAS-1440 in combination ... Oral administration of TAS-1440 at 50 mg/kg in HEL xenograft mouse model, showed a clear reduction of tumor growth after 21 days. In NCI-H1470 ...

4. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/tas-1440-taiho-pharmaceutical-refractory-acute-myeloid-leukemia-likelihood-of-approval/

TAS-1440 by Taiho Pharmaceutical for Refractory Acute ... According to GlobalData, Phase I drugs for Refractory Acute Myeloid Leukemia have a 68% phase transition success rate (PTSR) indication ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04282668/

Clinical Trial: NCT04282668 This is a multicenter, 2-part, Phase 1 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of TAS1440

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04282668

A Study of TAS1440 With ATRA in Subjects With r/r AML This is a multicenter, 2-part, Phase 1 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of TAS1440 ...

7. synapse.patsnap.com synapse.patsnap.com/drug/05e75d0407ce4892a5188bb73b42e761

TAS-1440 - Drug Targets, Indications, Patents A Phase 1 Study of Safety, Pharmacokinetics, and Preliminary Activity of TAS1440, as a Single Agent and in Combination With All-Trans Retinoic Acid (ATRA)

8. mycancergenome.org mycancergenome.org/content/drugs/TAS1440/

tas1440 Acute myeloid leukemia is the most common disease being investigated in tas1440 clinical trials [2]. Top Biomarker Inclusion Criteria for Open Clinical Trials ...