B-cell Small Lymphocytic Lymphoma RecurrentPhase 1NCT01317901
A Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma
A Phase 1 study testing TRU-016, Bendamustine and Rituximab in people with B-cell Small Lymphocytic Lymphoma Recurrent, run by Aptevo Therapeutics at 6 sites in United States.
Trial summary
This was a Phase 1 multicenter study of bendamustine, rituximab and TRU-016 (BRT) in subjects with relapsed indolent B-cell lymphoma. This was a multiple-dose escalation study to determine the maximum-tolerated dose (MTD) of TRU-016 given in combination with rituximab and bendamustine and to determine a safe dosing… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- B-cell Small Lymphocytic Lymphoma Recurrent
- What is being tested?
- TRU-016, Bendamustine and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 6 sitesUnited States
- Study dates
- May 2011to Jun 2013
- Phase
- Phase 1
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Histologically confirmed diagnosis of indolent non-Hodgkin's B-cell lymphoma (ie, follicular lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma) that has relapsed (relapsed is defined as confirmed progressive disease (PD) after receiving the most recent prior therapy, or failure to achieve at least a partial response (PR) while receiving the most recent prior therapy)
- At least one prior line of therapy for indolent lymphoma
- Bi-dimensionally measurable disease with at least one lesion measuring >=1.5 cm in a single dimension
- Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
- Creatinine clearance of >40 mL/min as calculated by the
Show all 11Show fewer
- Cockcroft-Gault method as follows:
- (140 - age) (weight in kg [ 0.85 if female] / 72 serum creatinine level) 7. Adequate hepatic function, indicated as follows:
- aspartate aminotransferase (AST) of <2.5 x upper limit of normal (ULN)
- alanine aminotransferase (ALT) of <2.5 x ULN
- total bilirubin of <= 1.5 x ULN 8. Absolute neutrophil count (ANC) >=1000/mm3 (1000/µL) 9. Platelet count >= 100,000/mm3 10. Female subjects of child-bearing potential and male subjects must use an acceptable form of birth control for the duration of their study participation and for 6 months after completing study drug dosing; acceptable forms of birth control, unless dictated otherwise by local regulatory authorities 11. For women of childbearing potential, a negative serum pregnancy test result obtained during the screening period and a negative urine pregnancy test result within 24 hours before first administration of study drug 12. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
Who cannot join
- Diagnosis of grade 3b follicular lymphoma or transformed lymphoma of any grade
- Previously received TRU-016
- Prior treatment with rituximab if subject discontinued rituximab due to unresolved toxicity
- Refractory to bendamustine, defined as follows:
- progression within 6 months of last dose of bendamustine
- failed to achieve at least a PR while receiving bendamustine
Show all 26Show fewer
- discontinued bendamustine due to toxicity
- received bendamustine within 6 months prior to first dose of study drug
- Received chemotherapy, radiotherapy, or immunotherapy including investigational agents within 28 days prior to the first dose of study drug
- Received therapeutic corticosteroids at doses equivalent to >10 mg prednisone per day for longer than 5 days within 14 days prior to the first dose of study drug, except if needed as a pre-medication
- Received filgrastim or equivalent within 14 days prior to screening (ie, collection of samples for laboratory tests) or pegfilgrastim within 28 days prior to screening (ie, collection of samples for laboratory tests)
- Prior allogeneic bone marrow transplant
- Prior autologous bone marrow transplant within 12 months prior to the first dose of study drug
- Received blood or platelet infusion within 7 days prior to screening (ie, collection of samples for laboratory tests)
- Previous or concurrent additional malignancy except non-invasive, non-melanomatous skin cancer or in situ carcinoma of the cervix, or other solid tumors if the subject has been disease-free for a minimum of 2 years prior to the first dose of study drug
- Known central nervous system or leptomeningeal lymphoma
- Any significant concurrent medical diseases or conditions, including but not limited to the following:
- Clinically significant pulmonary dysfunction requiring oxygen therapy
- An active infection (viral, bacterial, or fungal) requiring systemic therapy; subjects receiving prophylactic therapy are eligible
- Known allergy to mannitol
- History of positive serology for human immunodeficiency virus (HIV)
- Positive serology for hepatitis B (surface antigen or core antibody) Note: If a positive test result for hepatitis B core antibody is due to immunoglobulin treatment, the subject may be enrolled if the hepatitis B viral deoxyribonucleic acid (DNA) is negative.
- Positive serology for hepatitis C
- Pregnant or breastfeeding
- Other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with safety
- Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Site Reference ID/Investigator# 61542
Augusta, Georgia, 30912
Site Reference ID/Investigator# 61543
Birmingham, Alabama, 35294
Site Reference ID/Investigator# 61544
Chapel Hill, North Carolina, 27599-7305
Site Reference ID/Investigator# 61522
Hackensack, New Jersey, 07601
Site Reference ID/Investigator# 61523
Omaha, Nebraska, 68114
Site Reference ID/Investigator# 61524
Seattle, Washington, 98109-1023
About this study
Official title: A Phase 1 Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma
This was a Phase 1 multicenter study of bendamustine, rituximab and TRU-016 (BRT) in subjects with relapsed indolent B-cell lymphoma. This was a multiple-dose escalation study to determine the maximum-tolerated dose (MTD) of TRU-016 given in combination with rituximab and bendamustine and to determine a safe dosing regimen for the combination in up to 12 subjects with relapsed indolent lymphoma.
The originally planned Phase 2 portion, an open-label, randomized study to evaluate the efficacy of BRT compared with BR, was not conducted.
Read the detailed description
This study was planned to be conducted in 2 parts: a Phase 1b component designed to determine a safe dosing regimen, and a Phase 2 component designed to evaluate the efficacy of BRT compared to BR in subjects with relapsed indolent lymphoma. The Phase 2 component was not conducted.
This was an open-label, non randomized, multiple-dose escalation study to determine the MTD of BRT and to determine a safe dosing regimen for the combination in subjects with relapsed indolent lymphoma.
The study consisted of a screening period lasting up to 21 days, a treatment period lasting up to 6 cycles (28 days each), and a 60-day follow-up period. Up to 12 subjects (2 cohorts of 6 subjects each) were planned for enrollment. Two dose levels (10 and 20 mg/kg) of TRU-016 combined with rituximab 375 mg/m2 and bendamustine 90 mg/m2 were evaluated during up to 6 cycles (28 days each). TRU-016 was administered by intravenous (IV) infusion on Days 1 and 15 of each cycle. Rituximab was administered by IV infusion on Day 2 of each cycle. Bendamustine was administered by IV infusion on Days 1 and 2 of each cycle. Subjects received study treatment for up to 6 cycles.
- Being tested
- TRU-016, Bendamustine, Rituximab
- Keywords
- follicular lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, non-Hodgkin's lymphoma, indolent lymphoma
- Medical subject headings
- Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRU-016Drug
Also called otlertuzumab
100 mg TRU-016 lyophilized solution for infusion at 10 or 20 mg/kg (or 6 mg/kg, if necessary) on Days 1 and 15 of each 28 day cycle
BendamustineDrug
Also called Treanda
Bendamustine by IV administration on Days 1 and 2 of each 28 day cycle.
RituximabDrug
Also called rituxan
Rituximab by IV administration at 375 mg/m^2 on Day 2 of each 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| TRU-016+bendamustine+rituximab | Experimental | Two dose levels (10 and 20 mg/kg) of TRU 016 combined with rituximab 375 mg/m2 and bendamustine 90 mg/m2 were evaluated during up to 6 cycles (28 days each). TRU-016 was administered by intravenous (IV) infusion on Days 1 and 15 of each cycle. Rituximab was administered by IV infusion on Day 2 of each cycle. Bendamustine was administered by IV infusion on Days 1 and 2 of each cycle. Subjects received study treatment for up to 6 cycles. Receives: Drug: TRU-016; Drug: Bendamustine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response
Response was assessed by the investigator on the basis of clinical, radiological, and pathological (i.e., bone marrow) criteria, using the IWG criteria (Cheson et al 2007). A CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.
Measured: Day 15 and Day 28 of even-numbered cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2011 (estimated)
- Study startMay 2011
- Primary completionApr 2013
- Study completionJun 2013
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 B-cell Small Lymphocytic Lymphoma RecurrentStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aptevo Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Stromatt, MD, Study director, Aptevo Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01317901
- Sponsor's protocol ID
- 16011
- Status last verified
- Jun 2017
- First submitted
- 15 Mar 2011
- Last updated
- 28 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Gopal AK, Tarantolo SR, Bellam N, Green DJ, Griffin M, Feldman T, Mato AR, Eisenfeld AJ, Stromatt SC, Goy A. Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients. Invest New Drugs. 2014 Dec;32(6):1213-25. doi: 10.1007/s10637-014-0125-2. Epub 2014 Jun 15.
PubMed 24927856
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma
- ClinicalTrials.gov ID
- NCT01317901
- Acronym / sponsor ID
- 16011
- Keywords
- follicular lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, non-Hodgkin's lymphoma, indolent lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Aptevo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- May 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 17 Mar 2011 (estimated)
- Results
- Posted 6 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase 1 multicenter study of bendamustine, rituximab and TRU-016 (BRT) in subjects with relapsed indolent B-cell lymphoma. This was a multiple-dose escalation study to determine the maximum-tolerated dose (MTD) of TRU-016 given in combination with rituximab and bendamustine and to determine a safe dosing regimen for the combination in up to 12 subjects with relapsed indolent lymphoma.
The originally planned Phase 2 portion, an open-label, randomized study to evaluate the efficacy of BRT compared with BR, was not conducted.
Detailed description
This study was planned to be conducted in 2 parts: a Phase 1b component designed to determine a safe dosing regimen, and a Phase 2 component designed to evaluate the efficacy of BRT compared to BR in subjects with relapsed indolent lymphoma. The Phase 2 component was not conducted.
This was an open-label, non randomized, multiple-dose escalation study to determine the MTD of BRT and to determine a safe dosing regimen for the combination in subjects with relapsed indolent lymphoma.
The study consisted of a screening period lasting up to 21 days, a treatment period lasting up to 6 cycles (28 days each), and a 60-day follow-up period. Up to 12 subjects (2 cohorts of 6 subjects each) were planned for enrollment. Two dose levels (10 and 20 mg/kg) of TRU-016 combined with rituximab 375 mg/m2 and bendamustine 90 mg/m2 were evaluated during up to 6 cycles (28 days each). TRU-016 was administered by intravenous (IV) infusion on Days 1 and 15 of each cycle. Rituximab was administered by IV infusion on Day 2 of each cycle. Bendamustine was administered by IV infusion on Days 1 and 2 of each cycle. Subjects received study treatment for up to 6 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TRU-016+bendamustine+rituximab | Experimental | Drug: TRU-016, Drug: Bendamustine, Drug: RituximabTwo dose levels (10 and 20 mg/kg) of TRU 016 combined with rituximab 375 mg/m2 and bendamustine 90 mg/m2 were evaluated during up to 6 cycles (28 days each). TRU-016 was administered by intravenous (IV) infusion on Days 1 and 15 of each cycle. Rituximab was administered by IV infusion on Day 2 of each cycle. Bendamustine was administered by IV infusion on Days 1 and 2 of each cycle. Subjects received study treatment for up to 6 cycles. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18 years or older
- Histologically confirmed diagnosis of indolent non-Hodgkin's B-cell lymphoma (ie, follicular lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma) that has relapsed (relapsed is defined as confirmed progressive disease (PD) after receiving the most recent prior therapy, or failure to achieve at least a partial response (PR) while receiving the most recent prior therapy)
- At least one prior line of therapy for indolent lymphoma
- Bi-dimensionally measurable disease with at least one lesion measuring >=1.5 cm in a single dimension
- Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
Key exclusion criteria (26 listed)
- Diagnosis of grade 3b follicular lymphoma or transformed lymphoma of any grade
- Previously received TRU-016
- Prior treatment with rituximab if subject discontinued rituximab due to unresolved toxicity
- Refractory to bendamustine, defined as follows:
- Received chemotherapy, radiotherapy, or immunotherapy including investigational agents within 28 days prior to the first dose of study drug
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-016Also: otlertuzumab100 mg TRU-016 lyophilized solution for infusion at 10 or 20 mg/kg (or 6 mg/kg, if necessary) on Days 1 and 15 of each 28 day cycle | Drug | TRU-016+bendamustine+rituximab |
| BendamustineAlso: TreandaBendamustine by IV administration on Days 1 and 2 of each 28 day cycle. | Drug | TRU-016+bendamustine+rituximab |
| RituximabAlso: rituxanRituximab by IV administration at 375 mg/m^2 on Day 2 of each 28 day cycle. | Drug | TRU-016+bendamustine+rituximab |
Primary outcome
Response
Time frame: Day 15 and Day 28 of even-numbered cycles
Response was assessed by the investigator on the basis of clinical, radiological, and pathological (i.e., bone marrow) criteria, using the IWG criteria (Cheson et al 2007). A CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24927856Gopal AK, Tarantolo SR, Bellam N, Green DJ, Griffin M, Feldman T, Mato AR, Eisenfeld AJ, Stromatt SC, Goy A. Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients. Invest New Drugs. 2014 Dec;32(6):1213-25. doi: 10.1007/s10637-014-0125-2. Epub 2014 Jun 15.
- 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
Aptevo Therapeutics
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TRU-016, Bendamustine and Rituximab in people with B-cell Small Lymphocytic Lymphoma Recurrent, run by Aptevo Therapeutics at 6 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 11 inclusion and 26 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 28 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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?
Yes. Results are posted in the registry (first posted 6 Oct 2016). 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 (time frame: Day 15 and Day 28 of even-numbered cycles). 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 NCT01317901, 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 28 Jun 2017.