Clinical trial NCT01644253: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Peripheral T-cell Lymphoma
Keywords: chronic lymphocytic leukemia
CLL
previously untreated chronic lymphocytic leukemia
peripheral T-cell lymphoma
PTCL
Lead sponsor: Aptevo Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-07-19
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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:

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.

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

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: any time point during the study up to 18 months
measure: CLL Cysteine 481 mutation status
timeFrame: CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected.
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: any time point during the study up to 18 months
measure: Progression-free survival (PFS)
timeFrame: any time point during the study up to 18 months
measure: Overall survival (OS)
timeFrame: any time point during the study up to 18 months
measure: Duration of response (DOR)
timeFrame: any time point during the study up to 18 months
measure: Resolution of disease-related symptoms
timeFrame: any time point during the study up to 18 months
measure: Maximum serum drug concentration (Cmax)
timeFrame: any time point during the study up to 12 months
measure: Minimum serum drug concentration (Cmin)
timeFrame: any time point during the study up to 12 months
measure: Area under the concentration-time curve (AUC0-t and AUC0-∞)
timeFrame: any time point during the study up to 12 months
measure: Systemic clearance (CL)
timeFrame: any time point during the study up to 12 months
measure: Volume of distribution (Vd)
timeFrame: any time point during the study up to 12 months
measure: Elimination half-life (t1/2)
timeFrame: any time point during the study up to 12 months
Other outcomes:
Locations:
city: Augusta
country: United States
state: Georgia
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
facility: Eastern Regional Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute,1221 Madison St.
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Aptevo Therapeutics
name: Scott C. Stromatt, M.D.
role: STUDY_DIRECTOR
References: