A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid L… (NCT02807558) | Clinical Trial Compass
CompletedPhase 2
A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome
United States155 participantsStarted 2016-09-20
Plain-language summary
The purpose of this study is to determine the activity of tamibarotene in participants with relapsed/refractory (R/R) AML (administered as a monotherapy or in combination with azacitidine), R/R higher-risk MDS (HR-MDS) (administered as a monotherapy or in combination with daratumumab), newly diagnosed treatment naïve AML participants who are unlikely to tolerate standard intensive chemotherapy (administered as a monotherapy or in combination with azacitidine), or lower-risk MDS (LR-MDS) (administered as a monotherapy).
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Must have:
✓. Relapsed and/or refractory non-APL AML that has failed to achieve a complete remission (CR) or partial remission (PR) following standard induction therapy, or has relapsed after any duration of CR or PR i. Must have measurable disease with bone marrow blasts ≥5%at screening
✓. Relapsed and/or refractory HR-MDS (High / Very High Risk, as defined by the Revised International Prognostic Scoring System (IPSS-R)) that has failed to achieve a CR or PR, or any hematologic improvement (HI, per IWG 2006 criteria) after standard therapy with hypomethylating agents (e.g., azacitidine, decitabine), or has relapsed after any duration of CR or PR or HI i. Must have measurable disease with bone marrow blasts \>5% at screening
✓. Newly diagnosed, treatment-naïve non-APL AML in participants who, at the time of study entry are unlikely to tolerate standard intensive chemotherapy due to age, performance status, or comorbidities based on at least one of the following criteria:
✓. Transfusion-dependent LR-MDS without the del 5q abnormality, in participants refractory to erythropoietin treatment or unlikely to respond to erythropoietin treatment (EPO \>500).
✓. Participants must be evaluated for the RARA super-enhancer associated biomarker or RARA pathway associated biomarker at the time of study screening.
✓. Must be amenable to serial bone marrow aspirates and peripheral blood sampling during the study.
What they're measuring
1
Overall Response Rate (ORR) in Biomarker Positive AML or HR-MDS Participants Treated With Tamibarotene Monotherapy or in Combination With Azacitidine
Timeframe: Up to 48 months
2
Transfusion Independence Rate (TIR) for LR-MDS Participants Treated With Tamibarotene Monotherapy
Timeframe: Up to 48 months
3
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treated With Tamibarotene in Combination With Daratumumab
✓. ECOG Performance Status (PS) of 0, 1 or 2. For newly diagnosed AML participants \< 75 years of age, ECOG 0-3; for ≥ 75 years of age, ECOG 0-2.
Exclusion criteria
✕. Acute promyelocytic leukemia (APL, M3 subtype of AML) or participants with a t(9:22) cytogenetic translocation.
✕. Hyperleukocytosis (leukocytes ≥25 x 109/L) at study entry. The participants may be treated with hydroxyurea according to routine practice, and enroll in the study when the leukocyte count falls below 25 x 109/L.
✕. Participants known to be refractory to platelet or packed red cell transfusions per Institutional Guidelines, or a participant who refuses blood product support.
✕. Prior treatment with all-trans retinoic acid (ATRA) or systemic retinoid for the treatment of hematologic malignancy.
✕. Tamibarotene and daratumumab combination only - Prior or concurrent exposure to daratumumab or other CD38 therapies.
✕. Tamibarotene and daratumumab combination only - Participant has either of the following:
✕. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is \<50% of predicted normal.
✕. Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.