Chronic Lymphocytic Leukemia, Peripheral T-cell Lymphoma
Conditions
Keywords
chronic lymphocytic leukemia, CLL, previously untreated chronic lymphocytic leukemia, peripheral T-cell lymphoma, PTCL
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.
Interventions
BIOLOGICAL20 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
BIOLOGICAL10 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
BIOLOGICALTRU-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
BIOLOGICALTRU-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.
BIOLOGICALTRU-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.
BIOLOGICALTRU-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.
Sponsors
Aptevo Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events | any time point during the study up to 18 months | — |
| CLL Cysteine 481 mutation status | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) | any time point during the study up to 12 months | — |
| Overall Response Rate (ORR) | any time point during the study up to 18 months | — |
| Area under the concentration-time curve (AUC0-t and AUC0-∞) | any time point during the study up to 12 months | — |
| Systemic clearance (CL) | any time point during the study up to 12 months | — |
| Volume of distribution (Vd) | any time point during the study up to 12 months | — |
| Elimination half-life (t1/2) | any time point during the study up to 12 months | — |
| Minimum serum drug concentration (Cmin) | any time point during the study up to 12 months | — |
| Progression-free survival (PFS) | any time point during the study up to 18 months | — |
Countries
United States
Outcome results
None listed