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Chronic Lymphocytic LeukemiaPhase 1NCT01644253

Phase 1b Safety and Efficacy Study of TRU-016

A Phase 1 study testing 20 mg/kg TRU-016 + Rituximab, 10 mg/kg TRU-016 + Rituximab and TRU-016 20 mg/kg + Obinutuzumab in people with Chronic Lymphocytic Leukemia and Peripheral T-cell Lymphoma, run by Aptevo Therapeutics at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
20 mg/kg TRU-016 + Rituximab, 10 mg/kg TRU-016 + Rituximab and TRU-016 20 mg/kg + Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
8 sitesUnited States
Study dates
Sep 2012to 21 Apr 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites
  • Study site

    Augusta, Georgia, 30912

  • Study site

    Columbus, Ohio, 43210

  • Greenville Health System

    Greenville, South Carolina, 29605

  • Study site

    Houston, Texas, 77030

  • Eastern Regional Medical Center

    Philadelphia, Pennsylvania, 19124

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • Swedish Cancer Institute,1221 Madison St.

    Seattle, Washington, 98104

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Read the 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.
Being tested
20 mg/kg TRU-016 + Rituximab, 10 mg/kg TRU-016 + Rituximab, TRU-016 20 mg/kg + Obinutuzumab, TRU-016 6-20 mg/kg + idelalisib + rituximab, TRU-016 10-20 mg/kg + ibrutinib
Keywords
chronic lymphocytic leukemia, CLL, previously untreated chronic lymphocytic leukemia, peripheral T-cell lymphoma, PTCL
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, T-Cell, Peripheral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 20 mg/kg TRU-016 + RituximabBiological

    Also called Rituxan

    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

  • 10 mg/kg TRU-016 + RituximabBiological

    Also called Rituxan

    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

  • TRU-016 20 mg/kg + ObinutuzumabBiological

    Also called Gazyva

    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

  • TRU-016 6-20 mg/kg + idelalisib + rituximabBiological

    Also called Zydelig, Rituxan

    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.

  • TRU-016 10-20 mg/kg + ibrutinibBiological

    Also called Imbruvica

    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.

  • TRU-016 10-20 mg/kg + bendamustineBiological

    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.

Study groups in NCT01644253
Study groupRoleWhat they receive
Cohort 1 - Previously Untreated CLLExperimental20 mg/kg TRU-016 + Rituximab
Receives: Biological: 20 mg/kg TRU-016 + Rituximab
Cohort 2 - Relapsed CLLExperimental20 mg/kg TRU-016 + Rituximab
Receives: Biological: 20 mg/kg TRU-016 + Rituximab
Cohort 3 - Previously Untreated CLLExperimental10 mg/kg TRU-016 + Rituximab
Receives: Biological: 10 mg/kg TRU-016 + Rituximab
Cohort 4 - Previously Untreated CLLExperimental20 mg/kg TRU-016 20 + Obinutuzumab
Receives: Biological: TRU-016 20 mg/kg + Obinutuzumab
Cohort 5 - Relapse CLLExperimental20 mg/kg TRU-016 + idelalisib + rituximab
Receives: Biological: TRU-016 6-20 mg/kg + idelalisib + rituximab
Cohort 6 - With CLL on ibrutinib with no complete responseExperimental20 mg/kg TRU-016 + ibrutinib
Receives: Biological: TRU-016 10-20 mg/kg + ibrutinib
Cohort 7 - With CLL on ibrutinib with stable diseaseExperimental20 mg/kg TRU-016 + ibrutinib
Receives: Biological: TRU-016 10-20 mg/kg + ibrutinib
Cohort 8 - With relapsed or refractory PTCLExperimental20 mg/kg TRU-016 + 90 mg/m2 bendamustine
Receives: Biological: TRU-016 10-20 mg/kg + bendamustine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and severity of adverse events

    Measured: any time point during the study up to 18 months

  2. CLL Cysteine 481 mutation status

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

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

Secondary outcomes (11)
  1. Overall Response Rate (ORR)

    Measured: any time point during the study up to 18 months

  2. Progression-free survival (PFS)

    Measured: any time point during the study up to 18 months

  3. Overall survival (OS)

    Measured: any time point during the study up to 18 months

  4. Duration of response (DOR)

    Measured: any time point during the study up to 18 months

  5. Resolution of disease-related symptoms

    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.

    Measured: any time point during the study up to 18 months

  6. Maximum serum drug concentration (Cmax)

    Measured: any time point during the study up to 12 months

  7. Minimum serum drug concentration (Cmin)

    Measured: any time point during the study up to 12 months

  8. Area under the concentration-time curve (AUC0-t and AUC0-∞)

    Measured: any time point during the study up to 12 months

  9. Systemic clearance (CL)

    Measured: any time point during the study up to 12 months

  10. Volume of distribution (Vd)

    Measured: any time point during the study up to 12 months

  11. Elimination half-life (t1/2)

    Measured: any time point during the study up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2012 (estimated)
  2. Study startSep 2012
  3. Primary completion24 Feb 2020
  4. Study completion21 Apr 2021

Why it stopped: Business decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01644253
Sponsor's protocol ID
16009
Status last verified
May 2021
First submitted
12 Jul 2012
Last updated
20 May 2021
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 20 mg/kg TRU-016 + Rituximab, 10 mg/kg TRU-016 + Rituximab and TRU-016 20 mg/kg + Obinutuzumab in people with Chronic Lymphocytic Leukemia and Peripheral T-cell Lymphoma, run by Aptevo Therapeutics at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (time frame: any time point during the study up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2021.

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