Phase 1b Safety and Efficacy Study of TRU-016

NCT01644253 | Terminated Phase 1

• 1 other identifier: 16009
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 8

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.

Conditions

Chronic Lymphocytic Leukemia; Peripheral T-cell Lymphoma

Keywords

chronic lymphocytic leukemia; CLL; previously untreated chronic lymphocytic leukemia; peripheral T-cell lymphoma; PTCL

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events

  any time point during the study up to 18 months

• CLL Cysteine 481 mutation status

  The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone (\<1%).

  CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected.

Secondary Outcomes (11)

• Overall Response Rate (ORR)

  any time point during the study up to 18 months

• Progression-free survival (PFS)

  any time point during the study up to 18 months

• Overall survival (OS)

  any time point during the study up to 18 months

• Duration of response (DOR)

  any time point during the study up to 18 months

• Resolution of disease-related symptoms

  any time point during the study up to 18 months

Study Arms (8)

Cohort 1 - Previously Untreated CLL

EXPERIMENTAL

20 mg/kg TRU-016 + Rituximab

Biological: 20 mg/kg TRU-016 + Rituximab

Cohort 2 - Relapsed CLL

EXPERIMENTAL

20 mg/kg TRU-016 + Rituximab

Biological: 20 mg/kg TRU-016 + Rituximab

Cohort 3 - Previously Untreated CLL

EXPERIMENTAL

10 mg/kg TRU-016 + Rituximab

Biological: 10 mg/kg TRU-016 + Rituximab

Cohort 4 - Previously Untreated CLL

EXPERIMENTAL

20 mg/kg TRU-016 20 + Obinutuzumab

Biological: TRU-016 20 mg/kg + Obinutuzumab

Cohort 5 - Relapse CLL

EXPERIMENTAL

20 mg/kg TRU-016 + idelalisib + rituximab

Biological: TRU-016 6-20 mg/kg + idelalisib + rituximab

Cohort 6 - With CLL on ibrutinib with no complete response

EXPERIMENTAL

20 mg/kg TRU-016 + ibrutinib

Biological: TRU-016 10-20 mg/kg + ibrutinib

Cohort 7 - With CLL on ibrutinib with stable disease

EXPERIMENTAL

20 mg/kg TRU-016 + ibrutinib

Biological: TRU-016 10-20 mg/kg + ibrutinib

Cohort 8 - With relapsed or refractory PTCL

EXPERIMENTAL

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

Biological: TRU-016 10-20 mg/kg + bendamustine

Interventions

20 mg/kg TRU-016 + Rituximab BIOLOGICAL

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

Also known as: Rituxan

Cohort 1 - Previously Untreated CLL; Cohort 2 - Relapsed CLL

10 mg/kg TRU-016 + Rituximab BIOLOGICAL

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

Also known as: Rituxan

Cohort 3 - Previously Untreated CLL

TRU-016 20 mg/kg + Obinutuzumab BIOLOGICAL

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

Also known as: Gazyva

Cohort 4 - Previously Untreated CLL

TRU-016 6-20 mg/kg + idelalisib + rituximab BIOLOGICAL

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.

Also known as: Zydelig, Rituxan

Cohort 5 - Relapse CLL

TRU-016 10-20 mg/kg + ibrutinib BIOLOGICAL

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.

Also known as: Imbruvica

Cohort 6 - With CLL on ibrutinib with no complete response; Cohort 7 - With CLL on ibrutinib with stable disease

TRU-016 10-20 mg/kg + bendamustine BIOLOGICAL

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.

Cohort 8 - With relapsed or refractory PTCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aptevo Therapeutics: lead

Study Sites (8)

Unknown Facility

Augusta, Georgia, 30912, United States

Location

Unknown Facility

Columbus, Ohio, 43210, United States

Location

Eastern Regional Medical Center

Philadelphia, Pennsylvania, 19124, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute,1221 Madison St.

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, T-Cell, Peripheral

Interventions

TRU 016; Rituximab; obinutuzumab; idelalisib; ibrutinib; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Scott C. Stromatt, M.D.

  Aptevo Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: July 19, 2012
• Study Start: September 1, 2012
• Primary Completion: February 24, 2020
• Study Completion: April 21, 2021
• Last Updated: May 20, 2021

Record last verified: 2021-05

Locations

US (8)