Patient case: 26-year-old male with Liposarcoma. Genetic variant: MDM2 Amplification. Other conditions: None.

Clinical trial: A Dose Escalation and Cohort Expansion Study of RO6870810/TEN-010 in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome

Summary: TEN-010 is a small molecule, bromodomain and extra-terminal domain (BET) bromodomain inhibitor. This study is designed to characterize the safety, tolerability, and pharmacokinetics of TEN-010 in patients with relapsed/refractory acute myeloid leukemia (RR-AML) and hypomethylating agent (HMA)-refractory myelodysplastic syndrome (MDS). In addition, this trial will assess response to treatment using International Working Group (IWG) response criteria. This study will be conducted in two parts: dose escalation and dose expansion. For dose escalation (Part A), a standard "3+3" design will be used in which successive cohorts of three or more patients with RR-AML or HMA-refractory MDS will be treated at escalating doses until a maximum tolerated dose (MTD) is identiﬁed. For the dose expansion part of the study (Part B), patients will be treated with TEN-010 at the MTD (or the highest dose tested if the MTD is not deﬁned) to further characterize its safety, pharmacokinetics, and clinical response. A maximum of 68 patients aged 18 years or older with RR-AML or HMA-refractory MDS will be enrolled in the study. In part A, up to 18 adult patients will be enrolled. This includes up to 18 RR-AML or HMA-refractory MDS patients enrolled in 3 dose levels of up to 6 patients each. In part B, up to 50 patients with RR-AML and HMA-refractory MDS will be enrolled in separate study groups of up to 25 patients each.


Eligibility: Inclusion Criteria:
  -  Relapsed/refractory acute myeloid leukemia (AML)
  -  Relapsed/refractory myelodysplastic syndrome (MDS)
  -  Subjects with a history of allogeneic stem cell transplant are eligible for study participation provided the following eligibility criteria are met:
  1. Transplant was > 100 days prior to study enrollment
  2. Subject has not taken immunosuppressive medications for at least two weeks
  3. No signs or symptoms of graft versus host disease other than Grade 1 skin involvement
  4. No active infection
  -  ECOG performance status of <=2
  -  Life expectancy of at least 2 months
  -  Disease-free of active second/secondary or prior malignancies for >=1 year with the exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast
  -  Adequate hematological, renal, hepatic and coagulation laboratory test results
  -  Women of child bearing potential and men must agree to use adequate contraception during the study and for 4 months after the last dose of the study drug
  -  Available for the duration of the study and willing to follow study procedures
  Exclusion Criteria:
  -  NYHA Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia
  -  Have QTcF > 470 msec (female) or > 450 (male), or history of congenital long QT syndrome
  -  Uncontrolled bacterial, viral, or fungal infections
  -  Known clinically important respiratory impairment
  -  Positive for HIV, hepatitis B surface antigen, or hepatitis C antibodies
  -  History of major organ transplant
  -  Symptomatic CNS disease, malignancy, or metastasis
  -  Pregnant or nursing
  -  Concomitant chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy
  -  Treatment with surgery or chemotherapy within 21 days prior to study entry
  -  Prior treatment with small molecule (BET) family inhibitor
  -  Radiation for symptomatic lesions within 14 days of study enrollment
  -  Other exclusions apply

Relevance to patient case: not relevant