Chronic Lymphocytic Leukemia (CLL)Phase 1/2NCT01188681
Safety and Efficacy Study of TRU-016 Plus Bendamustine vs. Bendamustine in Relapsed Chronic Lymphocytic Leukemia
A Phase 1/2 study testing TRU-016 and bendamustine, Bendamustine and 15 mg/kg TRU-016 and bendamustine in people with Chronic Lymphocytic Leukemia (CLL), run by Aptevo Therapeutics at 25 sites in 5 countries.
Trial summary
The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL)
- What is being tested?
- TRU-016 and bendamustine, Bendamustine and 15 mg/kg TRU-016 and bendamustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 25 sitesin 5 countries
- Study dates
- Sep 2010to Dec 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 relapsed CLL with 1 to 3 prior treatments
- Demonstrated active disease requiring treatment
- No prior bendamustine treatment
- Not refractory to fludarabine or other purines, either as a single agent or in combination
- Age >/=18 years; male or female
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
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- Creatinine clearance > 40 mL/min
- Absolute neutrophil count (ANC) >/= 1,200/mm3
- Platelets >/= 75,000/mm3
- Lymphocytes >/= 5,000/mm3 in Phase 1b
Who cannot join
- Treatment with rituximab or other B-cell depleting agent within 30 days or alemtuzumab within 12 weeks
- Previous anticancer therapy within 30 days
- Refractory to prior fludarabine or other purine analog therapy either as a single agent or in combination
- Receipt of prior bendamustine or TRU-016
- Receipt of an investigational therapy or major surgery within 30 days
- Previous or concurrent additional malignancy (some exceptions apply)
Show all 11Show fewer
- Any significant concurrent medical diseases or conditions
- Positive serology for HIV or hepatitis C, hepatitis B surface antigen positive or hepatitis B core antibody positive.
- Pregnant or breast feeding
- Drug or alcohol abuse
- Allergic to mannitol
Trial locations and contacts
25 sites in 5 countries.
25 sites in 5 countries
United States9 sites
For additional information regarding sites for this trial call (919) 465-4648
Augusta, Georgia, 30912
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Chicago, Illinois, 60637
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Cleveland, Ohio, 44195
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Columbus, Ohio, 43210
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Denver, Colorado, 80218
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Durham, North Carolina, 27710
For additional information regarding sites for this trial call (919) 465-4648
Hackensack, New Jersey, 07601
For additional information regarding sites for this trial call (919) 465-4648
Seattle, Washington, 98109
For additional information regarding sites for this trial call (919) 465-4648
Syracuse, New York, 13210
Germany8 sites
For additional information regarding sites for this trial call (919) 465-4648
Bremen
For additional information regarding sites for this trial call (919) 465-4648
Cologne
For additional information regarding sites for this trial call (919) 465-4648
Frankfurt
For additional information regarding sites for this trial call (919) 465-4648
Göttingen
For additional information regarding sites for this trial call (919) 465-4648
Kiel
For additional information regarding sites for this trial call (919) 465-4648
Mainz
For additional information regarding sites for this trial call (919) 465-4648
Mutlangen
For additional information regarding sites for this trial call (919) 465-4648
Regensburg
Poland5 sites
For additional information regarding sites for this trial call (919) 465-4648
Bialystok
For additional information regarding sites for this trial call (919) 465-4648
Gdansk
For additional information regarding sites for this trial call (919) 465-4648
Lodz
For additional information regarding sites for this trial call (919) 465-4648
Poznan
For additional information regarding sites for this trial call (919) 465-4648
Warsaw
Spain2 sites
For additional information regarding sites for this trial call (919) 465-4648
Madrid
For additional information regarding sites for this trial call (919) 465-4648
Navarre
Austria1 site
For additional information regarding sites for this trial call (919) 465-4648
Vienna
About this study
Official title: A Phase 1b/2 Open Label Study to Evaluate the Safety and Efficacy of TRU-016 in Combination With Bendamustine vs. Bendamustine Alone in Patients With Relapsed Chronic Lymphocytic Leukemia
The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in patients with relapsed CLL.
Read the detailed description
This study consisted of two parts. The initial dose escalation stage was a Phase 1b study evaluating the safety and tolerability of two doses of TRU-016 administered in combination with bendamustine to patients with relapsed chronic lymphocytic leukemia (CLL). In the randomized Phase 2 stage of the study, the efficacy and safety of the selected dose of 20 mg/kg TRU-016 combined with bendamustine was compared to bendamustine alone. The pharmacokinetics and pharmacodynamics of TRU-016 and the development of antibodies to TRU-016 were evaluated in both phases of the study.
- Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Being tested
- TRU-016 and bendamustine, Bendamustine, 15 mg/kg TRU-016 and bendamustine, 20 mg/kg TRU-016 and bendamustine
- Keywords
- CLL, TRU-016, chronic lymphocytic leukemia, relapsed CLL, bendamustine
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRU-016 and bendamustineDrug
TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles
BendamustineDrug
Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles
15 mg/kg TRU-016 and bendamustineDrug
TRU-016 at 15 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles
20 mg/kg TRU-016 and bendamustineDrug
TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: 15 mg/kg TRU-016 + Bendamustine | Experimental | TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients Receives: Drug: 15 mg/kg TRU-016 and bendamustine |
| Phase 1: 20 mg/kg TRU-016 + Bendamustine | Experimental | TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients Receives: Drug: 20 mg/kg TRU-016 and bendamustine |
| Phase 2: TRU-016 and bendamustine | Experimental | TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients Receives: Drug: TRU-016 and bendamustine |
| Phase 2: Bendamustine | Active comparator | Bendamustine (70 mg/m2), n = 33 patients Receives: Drug: Bendamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
Patients had full clinical response assessment monthly during treatment, at the end of treatment (EOT) visit, 30 and 60 days after the EOT visit, and subsequently every 3 months until the earliest of progression of CLL, death, initiation of new therapy, withdrawal from the study, or completion of 18 months of follow-up evaluations. Clinical response assessment included physical examination with measurement of spleen, liver, and lymph nodes, disease-related symptoms, and laboratory measurements, specifically complete blood count (CBC) with differential.
Measured: 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years
Secondary outcomes (1)
Response Per NCI Criteria
Overall response rate per National Cancer Institute (NCI) Working group criteria.
Measured: 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2010 (estimated)
- Study startSep 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aptevo Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Stromatt, MD, Study director, Emergent Product Development Seattle LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01188681
- Sponsor's protocol ID
- 16201
- Status last verified
- May 2021
- First submitted
- 20 Aug 2010
- Last updated
- 10 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Robak T, Hellmann A, Kloczko J, Loscertales J, Lech-Maranda E, Pagel JM, Mato A, Byrd JC, Awan FT, Hebart H, Garcia-Marco JA, Hill BT, Hallek M, Eisenfeld AJ, Stromatt SC, Jaeger U. Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia. Br J Haematol. 2017 Feb;176(4):618-628. doi: 10.1111/bjh.14464. Epub 2016 Dec 15.
PubMed 27977057
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Open Label Study to Evaluate the Safety and Efficacy of TRU-016 in Combination With Bendamustine vs. Bendamustine Alone in Patients With Relapsed Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01188681
- Acronym / sponsor ID
- 16201
- Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Keywords
- CLL, TRU-016, chronic lymphocytic leukemia, relapsed CLL, bendamustine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Aptevo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 25 Aug 2010 (estimated)
- Results
- Posted 6 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in patients with relapsed CLL.
Detailed description
This study consisted of two parts. The initial dose escalation stage was a Phase 1b study evaluating the safety and tolerability of two doses of TRU-016 administered in combination with bendamustine to patients with relapsed chronic lymphocytic leukemia (CLL). In the randomized Phase 2 stage of the study, the efficacy and safety of the selected dose of 20 mg/kg TRU-016 combined with bendamustine was compared to bendamustine alone. The pharmacokinetics and pharmacodynamics of TRU-016 and the development of antibodies to TRU-016 were evaluated in both phases of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1: 15 mg/kg TRU-016 + Bendamustine | Experimental | Drug: 15 mg/kg TRU-016 and bendamustineTRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients |
| Phase 1: 20 mg/kg TRU-016 + Bendamustine | Experimental | Drug: 20 mg/kg TRU-016 and bendamustineTRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients |
| Phase 2: TRU-016 and bendamustine | Experimental | Drug: TRU-016 and bendamustineTRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients |
| Phase 2: Bendamustine | Active comparator | Drug: BendamustineBendamustine (70 mg/m2), n = 33 patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of relapsed CLL with 1 to 3 prior treatments
- Demonstrated active disease requiring treatment
- No prior bendamustine treatment
- Not refractory to fludarabine or other purines, either as a single agent or in combination
- Age >/=18 years; male or female
Key exclusion criteria (11 listed)
- Treatment with rituximab or other B-cell depleting agent within 30 days or alemtuzumab within 12 weeks
- Previous anticancer therapy within 30 days
- Refractory to prior fludarabine or other purine analog therapy either as a single agent or in combination
- Receipt of prior bendamustine or TRU-016
- Receipt of an investigational therapy or major surgery within 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TRU-016 and bendamustineTRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | Drug | Phase 2: TRU-016 and bendamustine |
| BendamustineBendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | Drug | Phase 2: Bendamustine |
| 15 mg/kg TRU-016 and bendamustineTRU-016 at 15 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | Drug | Phase 1: 15 mg/kg TRU-016 + Bendamustine |
| 20 mg/kg TRU-016 and bendamustineTRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | Drug | Phase 1: 20 mg/kg TRU-016 + Bendamustine |
Primary outcome
Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
Time frame: 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years
Patients had full clinical response assessment monthly during treatment, at the end of treatment (EOT) visit, 30 and 60 days after the EOT visit, and subsequently every 3 months until the earliest of progression of CLL, death, initiation of new therapy, withdrawal from the study, or completion of 18 months of follow-up evaluations. Clinical response assessment included physical examination with measurement of spleen, liver, and lymph nodes, disease-related symptoms, and laboratory measurements, specifically complete blood count (CBC) with differential.
1 secondary outcome
Response Per NCI Criteria
Time frame: 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27977057Robak T, Hellmann A, Kloczko J, Loscertales J, Lech-Maranda E, Pagel JM, Mato A, Byrd JC, Awan FT, Hebart H, Garcia-Marco JA, Hill BT, Hallek M, Eisenfeld AJ, Stromatt SC, Jaeger U. Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia. Br J Haematol. 2017 Feb;176(4):618-628. doi: 10.1111/bjh.14464. Epub 2016 Dec 15.
- Otlertuzumab and Bendamustine in Relapsed CLLLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Stromatt, MD study director
Emergent Product Development Seattle LLC
25 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TRU-016 and bendamustine, Bendamustine and 15 mg/kg TRU-016 and bendamustine in people with Chronic Lymphocytic Leukemia (CLL), run by Aptevo Therapeutics at 25 sites in 5 countries.
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 11 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: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Germany, Poland, Spain, Austria. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria (time frame: 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01188681, which also lists 1 linked publication.
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 10 Jun 2021.