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

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RO6870810
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana Farber Cancer Institute
  • Weill Cornell Medical College

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RO6870810

Arm Description

Participants with RR-AML and HMA-refractory MDS will receive RO6870810, as per schedule described in intervention description.

Outcomes

Primary Outcome Measures

Percentage of Participants With Dose-Limiting Toxicities (DLTs)
MTD of RO6870810
Percentage of Participants With Adverse Events (AEs)

Secondary Outcome Measures

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)
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)
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)

Full Information

First Posted
November 14, 2014
Last Updated
December 7, 2017
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02308761
Brief Title
A Study of RO6870810/TEN-010 in Participants With Acute Myeloid Leukemia and Myelodysplastic Syndrome
Official Title
A Dose Escalation Study of RO6870810/TEN-010 in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
November 6, 2014 (Actual)
Primary Completion Date
August 9, 2017 (Actual)
Study Completion Date
August 9, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RO6870810
Arm Type
Experimental
Arm Description
Participants with RR-AML and HMA-refractory MDS will receive RO6870810, as per schedule described in intervention description.
Intervention Type
Drug
Intervention Name(s)
RO6870810
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame
Cycle 1 (cycle length = 21 or 28 days)
Title
MTD of RO6870810
Time Frame
Cycle 1 (cycle length = 21 or 28 days)
Title
Percentage of Participants With Adverse Events (AEs)
Time Frame
Baseline up to 30 days after last dose (up to approximately 2.75 years)
Secondary Outcome Measure Information:
Title
Area Under the Concentration Versus Time Curve from Time Zero to the End of Dosing Interval 24 Hours Later (AUC0-24) of RO6870810
Description
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)
Time Frame
Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)
Title
Maximum Observed Plasma Concentration (Cmax) of RO6870810
Description
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)
Time Frame
Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)
Title
Time to Cmax (Tmax) of RO6870810
Description
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)
Time Frame
Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Transplant was more than (>) 100 days prior to study enrollment Participant has not taken immunosuppressive medications for at least 2 weeks No signs or symptoms of graft versus host disease other than Grade 1 skin involvement 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33586590
Citation
Roboz GJ, Desai P, Lee S, Ritchie EK, Winer ES, DeMario M, Brennan B, Nuesch E, Chesne E, Brennan L, Lechner K, Kornacker M, DeAngelo DJ. A dose escalation study of RO6870810/TEN-10 in patients with acute myeloid leukemia and myelodysplastic syndrome. Leuk Lymphoma. 2021 Jul;62(7):1740-1748. doi: 10.1080/10428194.2021.1881509. Epub 2021 Feb 13.
Results Reference
derived

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

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