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A Phase 1/2 study of Enzomenib (DSP-5336) in Adult Patients with Acute leukemia
EU CTIS ID: 2022-502741-10-00
What this study is testing
Phase 1: To assess the safety and tolerability of DSP-5336 monotherapy in patients with relapsed or refractory AML, ALL, or acute leukemia of ambiguous lineage. To determine the recommended Phase 2 dose (RP2D) of DSP-5336 based on the lowest dose of DSP-5336 that provides the maximum biologic and clinical effect, or the maximum tolerated dose (MTD), whichever is lower Phase 2: To evaluate the clinical activity of DSP-5336 monotherapy in patients with relapsed/refractory acute leukemia with an MLLr or patients with relapsed/refractory AML with an NPM1m
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- For patients in Phase 1: Have a confirmed diagnosis of refractory or relapsed AML, ALL, or acute leukemia of ambiguous lineage and whose disease has progressed after available standard therapies known to be active for their AML, ALL, or acute leukemia of ambiguous lineage. Participants must have a documented KMT2A (MLL) fusion or NPM1 mutation including those with coexisting FLT3 genomic alterations and/or IDH1/2 mutation.Participants who are candidates for stem cell transplantation must have been offered this therapeutic option
- For all patients: Have an estimated life expectancy ≥3 months, based on the investigator’s assessment
- For all patients: Females of childbearing potential must have a negative serum or urine pregnancy test.
- For all patients: Must agree to use one highly effective contraception method or 2 acceptable methods of birth control (each partner to use one method) or use prevention of pregnancy measures (ie, sexual abstinence, when this is the usual and preferred lifestyle of the patient) during the study and for 6 months (for females and males alike) after the last dose of study drug, if the male or female patient is of child-producing potential
- For all patients: Have bone marrow material suitable for genomic analysis (eg, MLLr or NPM1 mutations) of AML or ALL genetic alterations. Note: if a bone marrow material is insufficient, an alternative suitable tissue (eg, peripheral blood) must be provided.
- For patients in Phase 2: Have a confirmed diagnosis of refractory or relapsed AML or ALL according to WHO 2022 classification, as determined by pathology review at the treating institution, and who have ≥5% blasts by morphologic assessment in the bone marrow. Patients must have received clinically applicable standard therapies with confirmed survival benefit. Patients must not have had prior exposure to a menin inhibitor
You likely can't join if
- Have a histologic diagnosis of acute promyelocytic leukemia
- Have a cognitive, psychologic, or psychosocial impediment that would impair the ability of the patient to receive therapy according to the protocol, or adversely affect the ability of the patient to comply with the informed consent/assent process, protocol, or protocol-required visits and procedures
- Have a history of Grade ≥ 2 drug-induced interstitial lung disease or Grade ≥ 2 non-infectious pneumonitis within 6 months of starting study treatment.
- Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336.
- Receive concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5. Other antifungals that are used as standard of care to prevent or treat infections are permitted Note: If a patient is on one of the excluded azole class antifungals and can be switched to a permitted azole 7 or more days prior to study, that patient could be allowed on study (Arm B).
- Have a known detectable viral load for human immunodeficiency virus or hepatitis C, or evidence of a hepatitis B surface antigen, all being indicative of active infection.
See the full eligibility criteria
Who can join
- For patients in Phase 1: Have a confirmed diagnosis of refractory or relapsed AML, ALL, or acute leukemia of ambiguous lineage and whose disease has progressed after available standard therapies known to be active for their AML, ALL, or acute leukemia of ambiguous lineage. Participants must have a documented KMT2A (MLL) fusion or NPM1 mutation including those with coexisting FLT3 genomic alterations and/or IDH1/2 mutation.Participants who are candidates for stem cell transplantation must have been offered this therapeutic option
- For all patients: Have an estimated life expectancy ≥3 months, based on the investigator’s assessment
- For all patients: Females of childbearing potential must have a negative serum or urine pregnancy test.
- For all patients: Must agree to use one highly effective contraception method or 2 acceptable methods of birth control (each partner to use one method) or use prevention of pregnancy measures (ie, sexual abstinence, when this is the usual and preferred lifestyle of the patient) during the study and for 6 months (for females and males alike) after the last dose of study drug, if the male or female patient is of child-producing potential
- For all patients: Have bone marrow material suitable for genomic analysis (eg, MLLr or NPM1 mutations) of AML or ALL genetic alterations. Note: if a bone marrow material is insufficient, an alternative suitable tissue (eg, peripheral blood) must be provided.
- For patients in Phase 2: Have a confirmed diagnosis of refractory or relapsed AML or ALL according to WHO 2022 classification, as determined by pathology review at the treating institution, and who have ≥5% blasts by morphologic assessment in the bone marrow. Patients must have received clinically applicable standard therapies with confirmed survival benefit. Patients must not have had prior exposure to a menin inhibitor
- For patients in Phase 2: Have a documented KMT2A (MLL)-fusion or NPM1 mutation assessed at relapse or immediately prior to the determination of refractory status
- For all patients: Be ≥18 years of age
- For all patients: Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- For all patients: For DSP-5336 monotherapy, white blood cell (WBC) count must be below 30,000/μL at the time of enrollment and prior to starting study treatment. (Hydroxyurea and steroid for cytoreduction purpose will be allowed prior to enrollment and during study treatment).
- For all patients: Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia or neuropathy
- For all patients: Have adequate renal and hepatic function at Screening as determined by: a. Clearance of creatinine (CLcr) level ≥ 50 ml/min, assessed by the Cockcroft-Gault formula b. Total bilirubin ≤1.5 times the upper limit of normal (ULN) (or ≤2.0 times ULN for patients with known Gilbert’s syndrome) c. Aspartate aminotransferase (AST) ≤3.0 times ULN d. Alanine aminotransferase (ALT) ≤3.0 times ULN
- For all patients: Be willing to attend study visits as required by the protocol
What rules you out
- Have a histologic diagnosis of acute promyelocytic leukemia
- Have a cognitive, psychologic, or psychosocial impediment that would impair the ability of the patient to receive therapy according to the protocol, or adversely affect the ability of the patient to comply with the informed consent/assent process, protocol, or protocol-required visits and procedures
- Have a history of Grade ≥ 2 drug-induced interstitial lung disease or Grade ≥ 2 non-infectious pneumonitis within 6 months of starting study treatment.
- Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336.
- Receive concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5. Other antifungals that are used as standard of care to prevent or treat infections are permitted Note: If a patient is on one of the excluded azole class antifungals and can be switched to a permitted azole 7 or more days prior to study, that patient could be allowed on study (Arm B).
- Have a known detectable viral load for human immunodeficiency virus or hepatitis C, or evidence of a hepatitis B surface antigen, all being indicative of active infection.
- In the opinion of the treating investigator, have any concurrent conditions that could pose an undue medical hazard or interfere with interpretation of study results; these conditions include, but are not limited to: clinically significant non-healing or healing wounds; concurrent congestive heart failure (New York Heart Association Functional Classification Class III or IV; see Section 21.7); concurrent unstable angina; concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation); recent (within the prior 6 months) myocardial infarction; acute coronary syndrome within the previous 6 months; significant pulmonary disease (shortness of breath at rest or on mild exertion), eg, due to concurrent severe obstructive pulmonary disease, concurrent hypertension not controlled with concomitant medication, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 6 months.
- Have a history of Torsades de Pointes
- Have abnormal ECGs at screening that are clinically significant, such as QTc >480 with QTc corrected according to Fridericia’s formula [QTcF]).
- Are pregnant or breastfeeding or planning to become pregnant Note: Patients who are breastfeeding may be enrolled if they interrupt breastfeeding prior to the first dose of any study drugs and do not feed the baby with breast milk expressed after receiving the first dose of any study drugs. Breastfeeding should not be resumed for at least 6 months after the last dose of study drug. .
- Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336
- Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336.
- Received a donor lymphocyte infusion within 28 days prior to the first dose of DSP 5336, or receiving immunosuppressive therapy post-HSCT at the time of Screening, or with clinically active GVHD or GVHD requiring active medical intervention other than the use of topical steroids for ongoing cutaneous GVHD.
- Received antineoplastic agents (except hormonal therapies as adjuvant maintenance for breast or prostate cancers if a patient is taking before starting study treatment, and hydroxyurea given for controlling blast cells) or other investigational treatment within 14 days or 5 half-lives, whichever is shortest, prior to the first dose of DSP-5336
- Received systemic calcineurin inhibitors within 2 weeks prior to the first dose of DSP 5336
- Had major surgery within 28 days prior to the first dose of DSP-5336
- Have active central nervous system leukemia (prophylactic intrathecal chemotherapy is allowed).
- Have any history or complication of interstitial lung disease (for sites in Japan only) and, for clinical sites operating under the European Medicines Agencies, a history of Grade ≥ 2 drug-induced interstitial lung disease or Grade ≥ 2 non-infectious pneumonitis within 6 months of starting study treatment
- Have a known intolerance or hypersensitivity reaction to components of any of the investigational medicinal products
- Have a left ventricular ejection fraction (LVEF) <50%, as determined by ECHO
- Received antineoplastic agents (except hormonal therapies as adjuvant maintenance for breast or prostate cancers if a patient is taking before starting study treatment, and hydroxyurea given for controlling blast cells) or other investigational treatment within 14 days or 5 half-lives, whichever is shortest, prior to the first dose of DSP-5336 .
- Received systemic calcineurin inhibitors within 42 weeks prior to the first dose of DSP 5336.
- Have an active and uncontrolled, bacterial, viral, or fungal infection requiring parenteral therapy
- Have known 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
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- United Kingdom
- Korea, Republic of
- Taiwan
- Singapore
- United States
- Japan
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; United Kingdom; Korea, Republic of; Taiwan; Singapore; United States and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.