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New treatment option for Leukemia, Myeloid, Acute
Official title A Phase 1/2 Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia (Horizen-1)
ClinicalTrials.gov ID: NCT04988555
What this study is testing
What is Enzomenib?
Enzomenib is an investigational medicine, given as a pill taken by mouth, being studied as a potential treatment for leukemia, myeloid, acute.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 12 and older
You may be able to join if
- For patients in Phase I:
- Have a diagnosis of relapsed or refractory AML, ALL or acute leukemia of ambiguous lineage according to World Health Organization (WHO) 2022...
- Patients with MDS must have bone marrow blasts ≥ 5%
- Patients with MDS must have relapsed or refractory disease and have exhausted available standard therapies including at least 2 cycles of treatment...
- Have a confirmed diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) 2016 classification (Kumar, 2016) and whose...
You likely can't join if
- Has a left ventricular ejection fraction (LVEF) \<50%, as determined by ECHO
- Histological diagnosis of acute promyelocytic leukemia
- Received systemic calcineurin inhibitors within 2 weeks prior to the first dose of DSP 5336
- Have abnormal ECGs at screening that are clinically significant, such as (QTc \>480 msec, with QTc corrected according to Fridericia's formula...
- Has an active and uncontrolled, bacterial, viral, or fungal infection requiring parenteral therapy. Note: Patients must be afebrile with negative...
- Receives concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5, including specifically...
See the full eligibility criteria
Who can join
- For patients in Phase I:
- Have a diagnosis of relapsed or refractory AML, ALL or acute leukemia of ambiguous lineage according to World Health Organization (WHO) 2022 classification, or, in selected sites and regions, a diagnosis of MDS or MM as...
- Patients with MDS must have bone marrow blasts ≥ 5%
- Patients with MDS must have relapsed or refractory disease and have exhausted available standard therapies including at least 2 cycles of treatment with HMA For patients with MM (selected sites and regions):
- Have a confirmed diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) 2016 classification (Kumar, 2016) and whose disease has progressed after treatment with a minimum of 3 prior...
- Have measurable disease as defined in the protocol
- Meet the laboratory parameters set in the protocol For patients with relapsed/refractory AML in the venetoclax and azacitidine combination cohort (in countries and sites where permitted):
- Have MLLr or NPM1m. For patients with relapsed/refractory AML in the gilteritinib combination cohort (in countries and sites where permitted):
- Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836. For patients with relapsed/refractory AML with NPM1 enrolled in the RP2D confirmation cohort:
- Must have ≥5% blasts in bone marrow by morphologic assessment
- Must not have received prior treatment with a menin inhibitor For patients with newly diagnosed AML:
- Must have AML as defined by WHO 2022 criteria with a documented MLLr or NPM1m (patients with AML characterized by MLL partial tandem duplications, MLL deletions, or trisomy 11 are not eligible)
- Must not have received treatment for AML with the exception of hydroxyurea for control of white blood cell counts. For patients in Phase 2:
- Have a confirmed diagnosis of 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...
- Have a documented KMT2A (MLL)-fusion assessed at relapse or immediately prior to the determination of refractory status. KMT2A genetic alterations other than fusions (eg, KMT2A-PTD, amplification, point mutation) are...
- Be \> 18 years of age. For countries and sites where approved, for DSP-5336 monotherapy, acute leukemia patients ≥12 years of age who weigh ≥40 kg may be enrolled.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- For monotherapy, WBC below 30,000/μ at enrollment. For the combination arms, WBC count must be below 25,000/uL at enrollment and prior to starting treatment. (Hydroxyurea and steroids for cytoreduction purposes are...
- Clearance of creatinine level ≥ 50 ml/min, assessed by the CPK-EPI formula (2021 version and Cystatin C not required)
- Total bilirubin ≤1.5 the upper limit of normal (ULN) (or ≤2.0 ULN for patients with known Gilbert's syndrome)
- Aspartate aminotransferase (AST) ≤3.0 times ULN
- Alanine aminotransferase (ALT) ≤3.0 times ULN
- Any prior treatment-related toxicities resolved to Grade ≤1 prior to enrollment, with the exception of Grade ≤2 alopecia or neuropathy
- Be willing to attend study visits as required by the protocol
- Have an estimated life expectancy ≥3 months, based on the investigator's assessment
- 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...
- All men and all women of childbearing potential and male patients' partners who are women of childbearing potential are required to use a highly effective method of contraception during the study and for 6 months (for...
- Have AML/ALL/MDS/MM bone marrow material suitable for genomic analysis of AML,ALL, MDS, or MM genetic alterations. Note: If a bone marrow material is insufficient, an alternative suitable tissue (ex: peripheral blood)...
What rules you out
- Has a left ventricular ejection fraction (LVEF) \<50%, as determined by ECHO
- Histological diagnosis of acute promyelocytic leukemia
- Received systemic calcineurin inhibitors within 2 weeks prior to the first dose of DSP 5336
- Have abnormal ECGs at screening that are clinically significant, such as (QTc \>480 msec, with QTc corrected according to Fridericia's formula (QTcF). For clinical sites in the UK, have abnormal ECGs at screening that...
- Has an active and uncontrolled, bacterial, viral, or fungal infection requiring parenteral therapy. Note: Patients must be afebrile with negative blood cultures at least 72 hours prior to Cycle 1 Day 1.
- Receives concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5, including specifically: ketoconazole, isavuconazole and itraconazole. Other antifungals that are used as...
- Had major surgery within 28 days prior to the first dose of DSP-5336
- Has active central nervous system leukemia (prophylactic intrathecal chemotherapy is allowed).
- 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. For clinical sites in the UK, underwent CAR-T therapy or other...
- 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...
- 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)...
- 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...
- Have a known detectable viral load for human immunodeficiency virus or hepatitis C, or evidence of hepatitis B surface antigen, all being indicative of active infection. For sites in Japan, Taiwan, and Korea only...
- 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
- Have cognitive, psychological, 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...
- 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...
- Have any history or complication of interstitial lung disease (for sites in Japan in Phase 1 dose escalation). For clinical sites in the EU, have a history of Grade ≥ 2 drug-induced interstitial lung disease or Grade ≥...
- Have a history of Torsades de Pointes
- Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP-5336
- Have plasma cell leukemia (\>2.0 x 109 /L plasma cells in blood by standard differential) (for patients with MM)
- For patients intending to enroll into the combination cohort with gilteritinib: Patients must be gilteritinib-naïve or sensitive and have not received a FLT3 inhibitor in the relapsed refractory setting (prior FLT3...
- Have a known intolerance of hypersensitivity reaction to components of the investigational medicinal product
- For clinical sites in the UK: In Arm E (DSP-5336 + venetoclax/azacitidine), have received a live vaccine within 30 days prior to the first dose of DSP-5336
The study team makes the final eligibility decision.
Where it's taking place
- Newport Beach, California, United States
- Palo Alto, California, United States
- Denver, Colorado, United States
- Washington D.C., District of Columbia, United States
- Miami, Florida, United States
- Tampa, Florida, United States
- Chicago, Illinois, United States
- Baltimore, Maryland, United States
- Boston, Massachusetts, United States
- Morristown, New Jersey, United States
- New Brunswick, New Jersey, United States
- Buffalo, New York, United States
- New York, New York, United States
- Chapel Hill, North Carolina, United States
- Durham, North Carolina, United States
- Winston-Salem, North Carolina, United States
- Columbus, Ohio, United States
- Eugene, Oregon, United States
- Philadelphia, Pennsylvania, United States
- Pittsburgh, Pennsylvania, United States
+ 73 more site(s).
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, 12 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Newport Beach, California, United States; Palo Alto, California, United States; Denver, Colorado, United States; Washington D.C., District of Columbia, United States; Miami, Florida, United States; Tampa, Florida, United States and 87 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 ClinicalTrials.gov; the study team decides eligibility.