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Phase 1b Safety and Efficacy Study of TRU-016

Primary Purpose

Chronic Lymphocytic Leukemia, Peripheral T-cell Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
20 mg/kg TRU-016 + Rituximab
10 mg/kg TRU-016 + Rituximab
TRU-016 20 mg/kg + Obinutuzumab
TRU-016 6-20 mg/kg + idelalisib + rituximab
TRU-016 10-20 mg/kg + ibrutinib
TRU-016 10-20 mg/kg + bendamustine
Sponsored by
Aptevo Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring chronic lymphocytic leukemia, CLL, previously untreated chronic lymphocytic leukemia, peripheral T-cell lymphoma, PTCL

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of CLL by 2008 IWCLL criteria and with Rai stage intermediate or high risk CLL. Cohort 8 patients must have a diagnosis of PTCL.
  • No prior therapy for CLL for Cohorts 1, 3 and 4. For Cohort 2, 1-3 prior treatments. For Cohort 5, patients must have failed to respond or relapsed after 1 or more treatment regimens. For Cohort 6, patients who have been receiving ibrutinib for at least 12 months, have not had a CR, and in whom no cysteine 481 mutation is detected. For Cohort 7, patients who are receiving ibrutinib with stable disease and now have the cysteine 481 mutant clone present at levels of >1%. For Cohort 8, have refractory or relapsed PTCL after one or more prior therapies.
  • At least one of the following criteria for active disease requiring treatment: progressive splenomegaly and/or lymphadenopathy; anemia or thrombocytopenia due to bone marrow involvement; or progressive lymphocytosis with an increase of >50% over a 2-month period or an unanticipated doubling time of less than 6 months
  • For Cohorts 1, 3 and 4, contraindication to chemotherapy as first-line therapy due to patient age, comorbidity or patient preference
  • Age >/= to 18 years
  • ECOG performance status of </= 2
  • Life expectancy > 6 months in opinion of Investigator
  • Serum creatinine, total bilirubin, ALT/SGPT </= 2.0 x upper limit of normal
  • ANC >/= 800/mm3, Cohort 8 (PTCL): ANC >/= 1000/mm3
  • Platelets >/= 30,000/mm3

Exclusion Criteria:

  • For Cohorts 1, 3 and 4 only: Has received treatment with rituximab, alemtuzumab, ofatumumab or any other chemotherapeutic agent for CLL. Cohort 8: Received prior treatment with bendamustine and did not respond during treatment or relapsed less than sex months after completing treatment.
  • Has received an investigational therapy within 30 days of first dose of study drug
  • Previous or concurrent additional malignancy
  • Clinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune disease
  • Positive serology for HIV or hepatitis C
  • Hepatitis B surface antigen or hepatitis B core antibody positive
  • Pregnant or breastfeeding
  • Known current drug or alcohol abuse

Sites / Locations

  • Eastern Regional Medical Center
  • University of Pittsburgh
  • Greenville Health System
  • Swedish Cancer Institute,1221 Madison St.
  • Fred Hutchinson Cancer Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1 - Previously Untreated CLL

Cohort 2 - Relapsed CLL

Cohort 3 - Previously Untreated CLL

Cohort 4 - Previously Untreated CLL

Cohort 5 - Relapse CLL

Cohort 6 - With CLL on ibrutinib with no complete response

Cohort 7 - With CLL on ibrutinib with stable disease

Cohort 8 - With relapsed or refractory PTCL

Arm Description

20 mg/kg TRU-016 + Rituximab

20 mg/kg TRU-016 + Rituximab

10 mg/kg TRU-016 + Rituximab

20 mg/kg TRU-016 20 + Obinutuzumab

20 mg/kg TRU-016 + idelalisib + rituximab

20 mg/kg TRU-016 + ibrutinib

20 mg/kg TRU-016 + ibrutinib

20 mg/kg TRU-016 + 90 mg/m2 bendamustine

Outcomes

Primary Outcome Measures

Incidence and severity of adverse events
CLL Cysteine 481 mutation status
The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone (<1%).

Secondary Outcome Measures

Overall Response Rate (ORR)
Progression-free survival (PFS)
Overall survival (OS)
Duration of response (DOR)
Resolution of disease-related symptoms
Resolution of disease-related symptoms which are common to the disease include fever, weight loss, night sweats, fatigue, loss of appetite pain, and pruritus; symptoms will be assessed by descriptive statistics and data listings.
Maximum serum drug concentration (Cmax)
Minimum serum drug concentration (Cmin)
Area under the concentration-time curve (AUC0-t and AUC0-∞)
Systemic clearance (CL)
Volume of distribution (Vd)
Elimination half-life (t1/2)

Full Information

First Posted
July 12, 2012
Last Updated
May 18, 2021
Sponsor
Aptevo Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT01644253
Brief Title
Phase 1b Safety and Efficacy Study of TRU-016
Official Title
Phase 1b, Open Label Study to Evaluate Safety and Efficacy of TRU-016 in Combination With Rituximab, Obinutuzumab, Rituximab and Idelalisib, or Ibrutinib in Chronic Lymphocytic Leukemia and With Bendamustine in Peripheral T-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Terminated
Why Stopped
Business decision
Study Start Date
September 2012 (Actual)
Primary Completion Date
February 24, 2020 (Actual)
Study Completion Date
April 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aptevo Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of TRU-016 in combination with rituximab, in combination with obinutuzumab, in combination with rituximab and idelalisib, or in combination with ibrutinib in patients with CLL; and in combination with bendamustine in patients with PTCL.
Detailed Description
The study will consist of 8 dose cohorts: Previously untreated patients 20 mg/kg TRU-016 + rituximab. Relapsed patients, 20 mg/kg TRU-016 + rituximab. Previously untreated patients 10 mg/kg TRU-016 + rituximab. Previously untreated patients TRU-016 + obinutuzumab. Relapsed patients, 20 mg/kg TRU-016 + rituximab + idelalisib. Patients with CLL on ibrutinib or another BTK inhibitor for a total of more than 1 year who have not had a complete response (CR) will continue receiving ibrutinib or another BTK inhibitor. Patients with CLL on ibrutinib or another BTK inhibitor with stable disease and in whom the cysteine 481 mutant clone is present at a level >1%, will continue receiving ibrutinib or the alternative BTK inhibitor. Patients with relapsed or refractory PTCL will receive TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days) + bendamustine for 2 days every cycle for 6 cycles.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Peripheral T-cell Lymphoma
Keywords
chronic lymphocytic leukemia, CLL, previously untreated chronic lymphocytic leukemia, peripheral T-cell lymphoma, PTCL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 - Previously Untreated CLL
Arm Type
Experimental
Arm Description
20 mg/kg TRU-016 + Rituximab
Arm Title
Cohort 2 - Relapsed CLL
Arm Type
Experimental
Arm Description
20 mg/kg TRU-016 + Rituximab
Arm Title
Cohort 3 - Previously Untreated CLL
Arm Type
Experimental
Arm Description
10 mg/kg TRU-016 + Rituximab
Arm Title
Cohort 4 - Previously Untreated CLL
Arm Type
Experimental
Arm Description
20 mg/kg TRU-016 20 + Obinutuzumab
Arm Title
Cohort 5 - Relapse CLL
Arm Type
Experimental
Arm Description
20 mg/kg TRU-016 + idelalisib + rituximab
Arm Title
Cohort 6 - With CLL on ibrutinib with no complete response
Arm Type
Experimental
Arm Description
20 mg/kg TRU-016 + ibrutinib
Arm Title
Cohort 7 - With CLL on ibrutinib with stable disease
Arm Type
Experimental
Arm Description
20 mg/kg TRU-016 + ibrutinib
Arm Title
Cohort 8 - With relapsed or refractory PTCL
Arm Type
Experimental
Arm Description
20 mg/kg TRU-016 + 90 mg/m2 bendamustine
Intervention Type
Biological
Intervention Name(s)
20 mg/kg TRU-016 + Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
TRU-016: 10 mg/kg for first dose, all subsequent doses 20 mg/kg, IV once weekly for 8 weeks followed by 4 monthly doses Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV once weekly for 8 weeks followed by 4 monthly doses
Intervention Type
Biological
Intervention Name(s)
10 mg/kg TRU-016 + Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
TRU-016: 6 mg/kg for first dose, all subsequent doses 10 mg/kg, IV on Day 1, 8 and 15, followed by 5 monthly doses Rituximab: 375 mg/m2 for first dose, all subsequent doses 500 mg/m2, IV following TRU-016 schedule
Intervention Type
Biological
Intervention Name(s)
TRU-016 20 mg/kg + Obinutuzumab
Other Intervention Name(s)
Gazyva
Intervention Description
TRU-016: 6 mg/kg on Day 1, 20 mg/kg on Day 8 and 15, then 20 mg/kg once a month for 5 months Obinutuzumab: 100 mg on Day 1, 900 mg on Day 2, 1,000 mg on Day 8 and 15, then 1,000 mg once a month for 5 months
Intervention Type
Biological
Intervention Name(s)
TRU-016 6-20 mg/kg + idelalisib + rituximab
Other Intervention Name(s)
Zydelig, Rituxan
Intervention Description
TRU-016: 6 mg/kg on Days 15-36 weekly, 10 mg/kg on Days 43 and 50, then 20 mg/kg once a month for 5 months.
Intervention Type
Biological
Intervention Name(s)
TRU-016 10-20 mg/kg + ibrutinib
Other Intervention Name(s)
Imbruvica
Intervention Description
TRU-016: Dosed weekly for 8 weeks followed by 4 monthly intravenous (IV) infusions. The first dose will be 10 mg/kg and all subsequent doses will be 20 mg/kg.
Intervention Type
Biological
Intervention Name(s)
TRU-016 10-20 mg/kg + bendamustine
Intervention Description
TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days). Bendamustine (90 mg/m2 on days 2 and 3 of cycle 1 and then days 1 and 2 of cycles 2 to 6) will be infused after completion of TRU-016. If a patient is benefiting with stable disease or better, then TRU-016 may continue to be dosed every 3 weeks after the first 6 cycles; bendamustine will not be dosed beyond 6 cycles.
Primary Outcome Measure Information:
Title
Incidence and severity of adverse events
Time Frame
any time point during the study up to 18 months
Title
CLL Cysteine 481 mutation status
Description
The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone (<1%).
Time Frame
CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected.
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Time Frame
any time point during the study up to 18 months
Title
Progression-free survival (PFS)
Time Frame
any time point during the study up to 18 months
Title
Overall survival (OS)
Time Frame
any time point during the study up to 18 months
Title
Duration of response (DOR)
Time Frame
any time point during the study up to 18 months
Title
Resolution of disease-related symptoms
Description
Resolution of disease-related symptoms which are common to the disease include fever, weight loss, night sweats, fatigue, loss of appetite pain, and pruritus; symptoms will be assessed by descriptive statistics and data listings.
Time Frame
any time point during the study up to 18 months
Title
Maximum serum drug concentration (Cmax)
Time Frame
any time point during the study up to 12 months
Title
Minimum serum drug concentration (Cmin)
Time Frame
any time point during the study up to 12 months
Title
Area under the concentration-time curve (AUC0-t and AUC0-∞)
Time Frame
any time point during the study up to 12 months
Title
Systemic clearance (CL)
Time Frame
any time point during the study up to 12 months
Title
Volume of distribution (Vd)
Time Frame
any time point during the study up to 12 months
Title
Elimination half-life (t1/2)
Time Frame
any time point during the study up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of CLL by 2008 IWCLL criteria and with Rai stage intermediate or high risk CLL. Cohort 8 patients must have a diagnosis of PTCL. No prior therapy for CLL for Cohorts 1, 3 and 4. For Cohort 2, 1-3 prior treatments. For Cohort 5, patients must have failed to respond or relapsed after 1 or more treatment regimens. For Cohort 6, patients who have been receiving ibrutinib for at least 12 months, have not had a CR, and in whom no cysteine 481 mutation is detected. For Cohort 7, patients who are receiving ibrutinib with stable disease and now have the cysteine 481 mutant clone present at levels of >1%. For Cohort 8, have refractory or relapsed PTCL after one or more prior therapies. At least one of the following criteria for active disease requiring treatment: progressive splenomegaly and/or lymphadenopathy; anemia or thrombocytopenia due to bone marrow involvement; or progressive lymphocytosis with an increase of >50% over a 2-month period or an unanticipated doubling time of less than 6 months For Cohorts 1, 3 and 4, contraindication to chemotherapy as first-line therapy due to patient age, comorbidity or patient preference Age >/= to 18 years ECOG performance status of </= 2 Life expectancy > 6 months in opinion of Investigator Serum creatinine, total bilirubin, ALT/SGPT </= 2.0 x upper limit of normal ANC >/= 800/mm3, Cohort 8 (PTCL): ANC >/= 1000/mm3 Platelets >/= 30,000/mm3 Exclusion Criteria: For Cohorts 1, 3 and 4 only: Has received treatment with rituximab, alemtuzumab, ofatumumab or any other chemotherapeutic agent for CLL. Cohort 8: Received prior treatment with bendamustine and did not respond during treatment or relapsed less than sex months after completing treatment. Has received an investigational therapy within 30 days of first dose of study drug Previous or concurrent additional malignancy Clinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune disease Positive serology for HIV or hepatitis C Hepatitis B surface antigen or hepatitis B core antibody positive Pregnant or breastfeeding Known current drug or alcohol abuse
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott C. Stromatt, M.D.
Organizational Affiliation
Aptevo Therapeutics
Official's Role
Study Director
Facility Information:
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Eastern Regional Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19124
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Swedish Cancer Institute,1221 Madison St.
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Phase 1b Safety and Efficacy Study of TRU-016

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