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Phase 1b Safety and Efficacy Study of TRU-016 and Rituximab, Obinutuzumab, Idelalisib, or Ibrutinib in Chronic Lymphocytic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Aptevo Therapeutics
Sponsor:
Information provided by (Responsible Party):
Aptevo Therapeutics
ClinicalTrials.gov Identifier:
NCT01644253
First received: July 12, 2012
Last updated: September 14, 2016
Last verified: September 2016
  Purpose
The purpose of this study is to evaluate the safety and efficacy of TRU-016 when when administered in combination with rituximab or obinutuzumab, in combination with idelalisib and rituximab, or in combination with ibrutinib in patients with chronic lymphocytic leukemia (CLL).

Condition Intervention Phase
Chronic Lymphocytic Leukemia
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
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b, Open Label Study to Evaluate the Safety and Efficacy 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 Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Aptevo Therapeutics:

Primary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: any time point during the study up to 18 months ] [ Designated as safety issue: No ]
    ORR by the 2008 International Workshop on CLL (IWCLL) criteria

  • Cysteine 481 mutant clone [ Time Frame: any time point during the study ] [ Designated as safety issue: No ]
    The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone


Secondary Outcome Measures:
  • Safety [ Time Frame: any time point during the study up to 18 months ] [ Designated as safety issue: Yes ]
    The incidence and severity of adverse events, and changes from baseline in laboratory parameters, vital signs, and physical examination will be determined.

  • ORR [ Time Frame: any time point during the study up to 18 months ] [ Designated as safety issue: No ]
    ORR by 1996 NCI Working Group Criteria

  • Progression-free survival (PFS) [ Time Frame: any time point during the study up to 18 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: any time point during the study up to 18 months ] [ Designated as safety issue: No ]
  • Duration of response (DOR) [ Time Frame: any time point during the study up to 18 months ] [ Designated as safety issue: No ]
  • Resolution of disease-related symptoms [ Time Frame: Any time point during the study up to 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 123
Study Start Date: September 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CLL by 2008 IWCLL criteria and with Rai stage intermediate or high risk CLL
  • 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%.
  • 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
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01644253

Contacts
Contact: Jennifer Zovath 512 649 6619 jennifer.zovath@inventivhealth.com

Locations
United States, Georgia
For additional information regarding sites for this trial call (919) 465-4648 Completed
Augusta, Georgia, United States, 30912
United States, Ohio
For additional information regarding sites for this trial call (919) 465-4648 Recruiting
Columbus, Ohio, United States, 43210
Contact: Jennifer Zovath    512-649-6619    jennifer.zovath@inventivhealth.com   
Contact: Thomas Whitlow    614-688-9495      
United States, Texas
For additional information regarding sites for this trial call (919) 465-4648 Completed
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute,1221 Madison St. Recruiting
Seattle, Washington, United States, 98104
Contact: Donielle O'Connor    206-386-2444    donielle.o'connor@swedish.org   
Contact: Jennifer Zovath    614-688-9495    jennifer.zovath@inventivhealth.com   
Sponsors and Collaborators
Aptevo Therapeutics
Investigators
Study Director: Scott C. Stromatt, M.D. Aptevo Therapeutics
  More Information

Responsible Party: Aptevo Therapeutics
ClinicalTrials.gov Identifier: NCT01644253     History of Changes
Other Study ID Numbers: 16009 
Study First Received: July 12, 2012
Last Updated: September 14, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Aptevo Therapeutics:
chronic lymphocytic leukemia
CLL
previously untreated chronic lymphocytic leukemia

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

ClinicalTrials.gov processed this record on September 23, 2016