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Phase 1b Safety and Efficacy Study of TRU-016

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ClinicalTrials.gov Identifier: NCT01644253
Recruitment Status : Active, not recruiting
First Posted : July 19, 2012
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Aptevo Therapeutics

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Peripheral T-cell Lymphoma Biological: 20 mg/kg TRU-016 + Rituximab Biological: 10 mg/kg TRU-016 + Rituximab Biological: TRU-016 20 mg/kg + Obinutuzumab Biological: TRU-016 6-20 mg/kg + idelalisib + rituximab Biological: TRU-016 10-20 mg/kg + ibrutinib Biological: TRU-016 10-20 mg/kg + bendamustine Phase 1

Detailed Description:

The study will consist of 8 dose cohorts:

  1. Previously untreated patients 20 mg/kg TRU-016 + rituximab.
  2. Relapsed patients, 20 mg/kg TRU-016 + rituximab.
  3. Previously untreated patients 10 mg/kg TRU-016 + rituximab.
  4. Previously untreated patients TRU-016 + obinutuzumab.
  5. Relapsed patients, 20 mg/kg TRU-016 + rituximab + idelalisib.
  6. 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.
  7. 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.
  8. 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 123 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2012
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: Cohort 1 - Previously Untreated CLL
20 mg/kg TRU-016 + Rituximab
Biological: 20 mg/kg TRU-016 + Rituximab

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

Other Name: Rituxan

Experimental: Cohort 2 - Relapsed CLL
20 mg/kg TRU-016 + Rituximab
Biological: 20 mg/kg TRU-016 + Rituximab

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

Other Name: Rituxan

Experimental: Cohort 3 - Previously Untreated CLL
10 mg/kg TRU-016 + Rituximab
Biological: 10 mg/kg TRU-016 + Rituximab

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

Other Name: Rituxan

Experimental: Cohort 4 - Previously Untreated CLL
20 mg/kg TRU-016 20 + Obinutuzumab
Biological: TRU-016 20 mg/kg + Obinutuzumab

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

Other Name: Gazyva

Experimental: Cohort 5 - Relapse CLL
20 mg/kg TRU-016 + idelalisib + rituximab
Biological: TRU-016 6-20 mg/kg + idelalisib + rituximab
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.
Other Name: Zydelig, Rituxan

Experimental: Cohort 6 - With CLL on ibrutinib with no complete response
20 mg/kg TRU-016 + ibrutinib
Biological: TRU-016 10-20 mg/kg + ibrutinib
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.
Other Name: Imbruvica

Experimental: Cohort 7 - With CLL on ibrutinib with stable disease
20 mg/kg TRU-016 + ibrutinib
Biological: TRU-016 10-20 mg/kg + ibrutinib
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.
Other Name: Imbruvica

Experimental: Cohort 8 - With relapsed or refractory PTCL
20 mg/kg TRU-016 + 90 mg/m2 bendamustine
Biological: TRU-016 10-20 mg/kg + bendamustine
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 Measures :
  1. Incidence and severity of adverse events [ Time Frame: any time point during the study up to 18 months ]
  2. CLL Cysteine 481 mutation status [ Time Frame: CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected. ]
    The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone (<1%).


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: any time point during the study up to 18 months ]
  2. Progression-free survival (PFS) [ Time Frame: any time point during the study up to 18 months ]
  3. Overall survival (OS) [ Time Frame: any time point during the study up to 18 months ]
  4. Duration of response (DOR) [ Time Frame: any time point during the study up to 18 months ]
  5. Resolution of disease-related symptoms [ Time Frame: any time point during the study up to 18 months ]
    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.

  6. Maximum serum drug concentration (Cmax) [ Time Frame: any time point during the study up to 12 months ]
  7. Minimum serum drug concentration (Cmin) [ Time Frame: any time point during the study up to 12 months ]
  8. Area under the concentration-time curve (AUC0-t and AUC0-∞) [ Time Frame: any time point during the study up to 12 months ]
  9. Systemic clearance (CL) [ Time Frame: any time point during the study up to 12 months ]
  10. Volume of distribution (Vd) [ Time Frame: any time point during the study up to 12 months ]
  11. Elimination half-life (t1/2) [ Time Frame: any time point during the study up to 12 months ]


Information from the National Library of Medicine

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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:

  • 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

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): NCT01644253


Locations
United States, Georgia
Augusta, Georgia, United States, 30912
United States, Ohio
Columbus, Ohio, United States, 43210
United States, South Carolina
Greenville Health System
Greenville, South Carolina, United States, 29605
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute,1221 Madison St.
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Aptevo Therapeutics
Investigators
Study Director: Scott C. Stromatt, M.D. Aptevo Therapeutics

Responsible Party: Aptevo Therapeutics
ClinicalTrials.gov Identifier: NCT01644253     History of Changes
Other Study ID Numbers: 16009
First Posted: July 19, 2012    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018

Keywords provided by Aptevo Therapeutics:
chronic lymphocytic leukemia
CLL
previously untreated chronic lymphocytic leukemia
peripheral T-cell lymphoma
PTCL

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, Non-Hodgkin
Obinutuzumab
Idelalisib
Rituximab
Bendamustine Hydrochloride
Immunoglobulin G
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors