A Study of RO6870810/TEN-010 in Participants With Acute Myeloid Leukemia and Myelodysplastic Syndrome

Acute Myeloid Leukemia Clinical Trial

Official title:

A Dose Escalation Study of RO6870810/TEN-010 in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02308761
• Other study ID #: NP39142
• Status: Completed
• Phase: Phase 1
• First received: November 14, 2014
• Last updated: December 7, 2017
• Start date: November 6, 2014
• Est. completion date: August 9, 2017

Study information

• Verified date: December 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RO6870810 (formerly TEN-010) is a small molecule, bromodomain and extra-terminal (BET) bromodomain inhibitor. This study is designed to characterize the safety, tolerability, and pharmacokinetics of RO6870810 monotherapy in participants with relapsed/refractory acute myeloid leukemia (RR-AML) and hypomethylating agent (HMA)-refractory myelodysplastic syndrome (MDS). The study will consist of a Screening Period, Treatment Period, and Post-Treatment Period. A standard 3+3 design will be used in which successive cohorts of three or more participants with RR-AML or HMA-refractory MDS will be treated at escalating doses until a maximum tolerated dose (MTD) is identified. Up to 51 adult participants with AML or MDS will be enrolled in the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: August 9, 2017
• Est. primary completion date: August 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• RR-AML

• Relapsed/refractory MDS

• Participants with a history of allogeneic stem cell transplant are eligible for study participation provided the following eligibility criteria are met:

1. Transplant was more than (>) 100 days prior to study enrollment

2. Participant has not taken immunosuppressive medications for at least 2 weeks

3. No signs or symptoms of graft versus host disease other than Grade 1 skin involvement

4. No active infection

• Eastern Cooperative Oncology Group Performance Status score equal to or less than (<=) 2

• Life expectancy of at least 2 months

• Disease-free of active second/secondary or prior malignancies for equal to or more than (>=) 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 childbearing potential and men must agree to use adequate contraception from 28 days prior to the first dose of the study drug, during the entire Treatment Period, and for at least 28 days after the last dose of the study drug

Exclusion Criteria:

• New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia

• Have Fridericia-corrected QT interval > 470 milliseconds (msec) (female) or > 450 msec (male), or history of congenital long QT syndrome

• Uncontrolled bacterial, viral, or fungal infections

• Known clinically important respiratory impairment

• Positive for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C antibodies

• History of major organ transplant

• Symptomatic central nervous system 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 bromodomain and extra terminal family inhibitor

• Radiation for symptomatic lesions within 14 days of study enrollment

• Active substance abuse

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• RO6870810
Participants will receive RO6870810 once daily (at escalated doses) via subcutaneous injection in either 28-day cycles (continuous 28 days dosing or 21 days dosing followed by 7 days off drug) or in 21-day cycle (14 days dosing followed by 7 days off drug), until MTD is identified.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Weill Cornell Medical College	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose-Limiting Toxicities (DLTs)		Cycle 1 (cycle length = 21 or 28 days)
Primary	MTD of RO6870810		Cycle 1 (cycle length = 21 or 28 days)
Primary	Percentage of Participants With Adverse Events (AEs)		Baseline up to 30 days after last dose (up to approximately 2.75 years)
Secondary	Area Under the Concentration Versus Time Curve from Time Zero to the End of Dosing Interval 24 Hours Later (AUC0-24) of RO6870810	Predose (Hour 0), immediately postdose and 0.25, 0.5, 1, 2, 4 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 22 (Cycle 1 Day 22 is applicable only for 28-day continuous treatment); Predose (Hour 0), 4 hours postdose on Cycle 1 Day 2; Days 8, 15 of Cycle 1; Predose (Hour 0) on Day 1 of each treatment cycle from Cycle 2 up to end of treatment (approximately 2.75 years) (Cycle length = 21 or 28 days)	Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)
Secondary	Maximum Observed Plasma Concentration (Cmax) of RO6870810	Predose (Hour 0), immediately postdose and 0.25, 0.5, 1, 2, 4 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 22 (Cycle 1 Day 22 is applicable only for 28-day continuous treatment); Predose (Hour 0), 4 hours postdose on Cycle 1 Day 2; Days 8, 15 of Cycle 1; Predose (Hour 0) on Day 1 of each treatment cycle from Cycle 2 up to end of treatment (approximately 2.75 years) (Cycle length = 21 or 28 days)	Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)
Secondary	Time to Cmax (Tmax) of RO6870810	Predose (Hour 0), immediately postdose and 0.25, 0.5, 1, 2, 4 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 22 (Cycle 1 Day 22 is applicable only for 28-day continuous treatment); Predose (Hour 0), 4 hours postdose on Cycle 1 Day 2; Days 8, 15 of Cycle 1; Predose (Hour 0) on Day 1 of each treatment cycle from Cycle 2 up to end of treatment (approximately 2.75 years) (Cycle length = 21 or 28 days)	Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)