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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02308761
Recruitment Status : Completed
First Posted : December 4, 2014
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Drug: RO6870810 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dose Escalation Study of RO6870810/TEN-010 in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome
Actual Study Start Date : November 6, 2014
Actual Primary Completion Date : August 9, 2017
Actual Study Completion Date : August 9, 2017


Arm Intervention/treatment
Experimental: RO6870810
Participants with RR-AML and HMA-refractory MDS will receive RO6870810, as per schedule described in intervention description.
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.




Primary Outcome Measures :
  1. Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (cycle length = 21 or 28 days) ]
  2. MTD of RO6870810 [ Time Frame: Cycle 1 (cycle length = 21 or 28 days) ]
  3. 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 Measures :
  1. Area Under the Concentration Versus Time Curve from Time Zero to the End of Dosing Interval 24 Hours Later (AUC0-24) of RO6870810 [ Time Frame: Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome 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)

  2. Maximum Observed Plasma Concentration (Cmax) of RO6870810 [ Time Frame: Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome 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)

  3. Time to Cmax (Tmax) of RO6870810 [ Time Frame: Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome 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)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02308761


Locations
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United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02308761    
Other Study ID Numbers: NP39142
First Posted: December 4, 2014    Key Record Dates
Last Update Posted: December 11, 2017
Last Verified: December 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions