What is the mechanism of action of this treatment?

Common treatments for Acute Myeloid Leukemia (AML) include standard cytotoxic chemotherapy, such as cytarabine and anthracyclines, which work by damaging the DNA of rapidly dividing cells, leading to cell death. Targeted therapies, like FLT3 inhibitors and IDH inhibitors, specifically target mutated proteins that drive leukemia cell proliferation. Novel agents, such as DSP-5336, are designed to inhibit specific pathways or proteins involved in AML pathogenesis, potentially offering more precise and effective treatment options. These mechanisms are crucial for AML patients as they aim to eliminate leukemic cells while minimizing damage to normal cells, thereby improving remission rates and overall survival.

What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML), especially those targeting specific pathways or proteins, often come with a range of side effects. For instance, gilteritinib, an FLT3 inhibitor, can cause differentiation syndrome, posterior reversible encephalopathy syndrome (PRES), prolonged QT interval, and pancreatitis. General chemotherapy agents like cytarabine and daunorubicin can lead to myelosuppression, gastrointestinal issues, and increased risk of infections. Other targeted therapies may also cause specific toxicities related to their mechanisms of action, such as myelosuppression, gastrointestinal toxicity, and hepatic toxicity.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Acute Myeloid Leukemia (AML), particularly those targeting specific pathways or proteins. Hypomethylating agents such as azacitidine and decitabine have been approved for AML, especially in patients who are not candidates for intensive chemotherapy. Venetoclax, a BCL-2 inhibitor, has been approved in combination with hypomethylating agents for newly diagnosed AML in elderly patients or those unfit for intensive chemotherapy. Additionally, midostaurin, a FLT3 inhibitor, has been approved for AML with FLT3 mutations. These approvals highlight the trend towards targeted therapies and combination treatments in AML management.

What other types of research exist?

Promising novel alternatives to DSP-5336 for AML treatment include AEE788, a VEGF receptor tyrosine kinase inhibitor with antiproliferative and proapoptotic effects, and AKN-028, a potent FLT3 inhibitor that induces cell cycle arrest and downregulates Myc-associated genes. Additionally, AG636, an inhibitor of mitochondrial pyrimidine synthesis, and XIAP antisense therapy with AEG 35156, which has shown anti-leukemic activity in combination with standard chemotherapy, are also potential alternatives.

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DSP-5336 for Leukemia

Phase 1 & 2

Recruiting

Research Sponsored by Sumitomo Pharma America, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients in the Phase 2 dose-expansion portion must have a confirmed diagnosis of relapsed or refractory AML, as determined by pathology review at the treating institution, and who failed available standard therapies known to be active for their AML. They must also have a documented KMT2A (MLL)-fusion or NPM1 mutation, which includes those with coexisting FLT3 genomic alterations and/or IDH1/2 mutations.

Females of childbearing potential must have a negative serum pregnancy test. Females of childbearing potential are defined as women who have (1) experienced menarche and have not undergone sterilization procedures (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or have (2) not experienced menopause (defined as having amenorrhea continuously for more than 12 months that is not determined to be drug-induced, or who are taking hormone replacement therapy with serum follicle-stimulating hormone > 35 mlU/ml).

Must not have

Has immediately life threatening or severe complications of leukemia

Have severe dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally, including the inability to swallow oral medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 2 months after first dose

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called DSP 5336 to help treat adults with certain types of blood cancer that have come back or didn't respond to previous treatments. The study will first find the best amount to give and then check how safe and helpful it is.

Who is the study for?

This trial is for adults with relapsed or refractory Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL), who have failed standard treatments. Phase 1 includes those with certain genetic abnormalities, while Phase 2 requires a confirmed diagnosis of AML with specific mutations. Participants must be in good physical condition, not pregnant, and willing to use effective contraception.

What is being tested?

The study tests DSP-5336, a new drug for patients whose leukemia has returned after treatment or hasn't responded to previous therapies. It's conducted in two parts: first determining the right dose and then expanding that dose to more patients with particular genetic markers.

What are the potential side effects?

While the side effects of DSP-5336 are not explicitly listed here, similar drugs may cause nausea, fatigue, increased risk of infection due to low blood cell counts, liver issues, and potential allergic reactions among others.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have AML that didn't respond to treatment and have specific genetic changes.

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I am a woman who can have children and have a negative pregnancy test.

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I can do most of my daily activities without help.

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I am over 18 years old, or over 20 if my local laws require it.

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My kidneys are functioning well, with a creatinine clearance rate of 50 ml/min or higher.

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My leukemia cells can be tested for genetic changes.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My leukemia is causing severe or life-threatening issues.

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I cannot take pills due to severe swallowing or digestion issues.

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My heart's pumping ability is below normal.

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I do not have an active infection, including HIV, HBV, or HCV.

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I have not had major surgery in the last 4 weeks.

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My leukemia has spread to my brain or spinal cord.

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I have an ongoing serious infection needing treatment.

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I have another type of cancer that is spreading and not under control.

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I have had Torsades de Pointes in the past.

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I have been treated with menin-MLL inhibitors before.

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I had a stem cell transplant or CAR-T therapy within the last 2 months.

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My liver disease is severe (Child-Pugh Class B or worse).

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I have been diagnosed with acute promyelocytic leukemia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 2 months after first dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 2 months after first dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 2 months after first dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 2 To evaluate clinical activity of DSP-5336 in adult patients with Relapsed /refractory AML who have MLL (KRMa gene rearrangement or NPM1 gene mutation)

Phase I Assess the safety and tolerability of DSP-5336 in relapsed/refractory AML, ALL or acute leukemia of amibiguous lineage

Phase I Determine the RP2D based on lowest dose of DSP-5336 that provides the maximum biologic and clinical effect, or the MTD, whichever is lower.

Secondary study objectives

2. Phase 2 To further assess safety and tolerability of DSP-5336 in adult patients with Relapsed /refractory AML

Phase I Preliminary clinical activity of DSP-5336 in adult patients with AML or ALL

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Phase 2 Arm B: AML with NPM1c mutationsExperimental Treatment1 Intervention

Patients with R/R AML w/ NPM1c mutations

Group II: Phase 2 Arm A AML with MLL (KMT2A) gene rearrangementsExperimental Treatment1 Intervention

Patients with R/R AML w/MLL (KMT2A) gene rearrangements

Group III: Phase 1 Arm B with AntifungalsExperimental Treatment1 Intervention

Patients receiving anti-fungals that are moderate to strong cytochrome CYP3A4/5 inhibitors (i.e. Posaconazole, voriconazole, fluconazole, or isavuconazonium (prodrug of isavuconazole).

Group IV: Phase 1 Arm A without AntifungalsExperimental Treatment1 Intervention

Patients not taking antifungals within 7 days of study entry

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Acute Myeloid Leukemia (AML) include standard cytotoxic chemotherapy, such as cytarabine and anthracyclines, which work by damaging the DNA of rapidly dividing cells, leading to cell death. Targeted therapies, like FLT3 inhibitors and IDH inhibitors, specifically target mutated proteins that drive leukemia cell proliferation. Novel agents, such as DSP-5336, are designed to inhibit specific pathways or proteins involved in AML pathogenesis, potentially offering more precise and effective treatment options. These mechanisms are crucial for AML patients as they aim to eliminate leukemic cells while minimizing damage to normal cells, thereby improving remission rates and overall survival.

Immunotherapy in AML: a brief review on emerging strategies.Role of epigenetic in leukemia: From mechanism to therapy.Molecular targeting in acute myeloid leukemia.