RecruitingPhase 1/2

A Phase 1/2 Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia (Horizen-1)

United States606 participantsStarted 2022-02-28

Plain-language summary

A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.

Who can participate

Age range12 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. 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 determined by pathology review at the treating institution, and whose disease has progressed after available standard therapies known to be active for their AML, ALL, or acute leukemia of ambiguous lineage or, in selected sites and regions, for MM or MDS. If acute leukemia patients are transformation from MDS or other hematologic malignancies, patients need to receive available standard therapies as acute leukemia after AML transformation and before enrolling this trial. In regions or countries where required by regulatory authorities, 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.
✓. 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
✓. 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 anti-myeloma regimens including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody (mAb); patients must not be candidates for available therapies with established clinical benefit
✓. Have measurable disease as defined in the protocol
✓. Meet the laboratory parameters set in the protocol
✓. Have MLLr or NPM1m.
✓. Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.

Exclusion criteria

✕. 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 are clinically significant, such as QTc ≥470 msec and ≥450 msec with QTc corrected according to Fridericia's formula (QTcF), for females and males, respectively. In addition, patients with a history of prolonged QT syndrome or who are required to take therapies associated with QT-interval prolongation are excluded.
✕. 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 standard of care to prevent or treat infections are permitted. If a patient is on one of the excluded azole class antifungals, he/she can be taken off or switched to a permitted azole 7 or more days prior to first dose, then the patient could be allowed on study (Arm B) with approval of the medical monitor.
✕. 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).

What they're measuring

Number of patients with adverse events and serious adverse events in Phase 1

Timeframe: 30 days from last dose

Determination of Recommended Phase 2 Dose (RP2D)

Timeframe: Within 4 months from first dose

Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the combination venetoclax and azacitidine arm

Timeframe: Within 4 months from first dose

Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the gilteritinib arm

Timeframe: Within 4 months from first dose

Optimal dose of DSP-5336 (RP2D) for patients newly diagnosed with AML enrolled into the combination venetoclax and azacitidine arm

Timeframe: Within 4 months from the first dose

Determination of Recommended Phase 2 Dose (RP2D) for patients enrolled into the 7 + 3 arm

Timeframe: Within 4 months from first dose

Number of patients achieving complete response (CR) and complete response with partial hematologic recovery (CRh) in Phase 2

Timeframe: Approximately 6 months after first dose

Trial details

NCT IDNCT04988555

SponsorSumitomo Pharma America, Inc.

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2027-06-30

Contact for this trial

Matt Hitron, MD

508-481-6700 matthew.hitron@us.sumitomo-pharma.com

View on ClinicalTrials.gov More Leukemia, Myeloid, Acute trials

Who can participate

Age range12 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. 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 determined by pathology review at the treating institution, and whose disease has progressed after available standard therapies known to be active for their AML, ALL, or acute leukemia of ambiguous lineage or, in selected sites and regions, for MM or MDS. If acute leukemia patients are transformation from MDS or other hematologic malignancies, patients need to receive available standard therapies as acute leukemia after AML transformation and before enrolling this trial. In regions or countries where required by regulatory authorities, 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.
✓. 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
✓. 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 anti-myeloma regimens including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody (mAb); patients must not be candidates for available therapies with established clinical benefit
✓. Have measurable disease as defined in the protocol
✓. Meet the laboratory parameters set in the protocol
✓. Have MLLr or NPM1m.
✓. Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.

Exclusion criteria

✕. 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 are clinically significant, such as QTc ≥470 msec and ≥450 msec with QTc corrected according to Fridericia's formula (QTcF), for females and males, respectively. In addition, patients with a history of prolonged QT syndrome or who are required to take therapies associated with QT-interval prolongation are excluded.
✕. 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 standard of care to prevent or treat infections are permitted. If a patient is on one of the excluded azole class antifungals, he/she can be taken off or switched to a permitted azole 7 or more days prior to first dose, then the patient could be allowed on study (Arm B) with approval of the medical monitor.
✕. 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).

What they're measuring

Number of patients with adverse events and serious adverse events in Phase 1

Timeframe: 30 days from last dose

Determination of Recommended Phase 2 Dose (RP2D)

Timeframe: Within 4 months from first dose

Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the combination venetoclax and azacitidine arm

Timeframe: Within 4 months from first dose

Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the gilteritinib arm

Timeframe: Within 4 months from first dose

Optimal dose of DSP-5336 (RP2D) for patients newly diagnosed with AML enrolled into the combination venetoclax and azacitidine arm

Timeframe: Within 4 months from the first dose

Determination of Recommended Phase 2 Dose (RP2D) for patients enrolled into the 7 + 3 arm

Timeframe: Within 4 months from first dose

Number of patients achieving complete response (CR) and complete response with partial hematologic recovery (CRh) in Phase 2

Timeframe: Approximately 6 months after first dose