Diffuse Large B Cell LymphomaPhase 2S-BRNCT02623920
Brentuximab Vedotin, Bendamustine, and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
A Phase 2 study testing Brentuximab, Bendamustine and Rituximab in people with Diffuse Large B Cell Lymphoma and Mediastinal Large B-cell Lymphoma, run by University of Arizona at 1 site in United States.
Trial summary
This phase II trial studies how well brentuximab vedotin, bendamustine, and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma, Mediastinal Large B-cell Lymphoma, Grey Zone Lymphoma
- What is being tested?
- Brentuximab, Bendamustine and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2015to 17 May 2017
- Phase
- Phase 2
- 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
- CD30 detectable B lineage relapsed refractory NHL including the following histologies:
- Aggressive lymphomas: diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, grey zone lymphomas, high grade B cell lymphomas, and transformed indolent lymphomas
- Indolent lymphoma: follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma; indolent lymphoma patients eligible for this trial should have high tumor burden and high risk disease, as defined by:
- The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
- Intermediate or high risk by Follicular Lymphoma International Prognostic Index (FLIPI) score or elevated lactose dehydrogenase (LDH)/ beta-2 microglobulin (B2M)
- Subjects between 18 and 75 years old. Subjects older than 75 years old to be discussed with PI prior to subject consent; consensus between PI and treating physician is required.
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- Karnofsky performance status (KPS) >= 70%, Eastern Cooperative Oncology Group (ECOG) =< 2
- At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
- Patients must have received at least one but no more than 4 prior lines of systemic therapy
- American Heart Association (AHA) class 1 without significant limitation of physical activity
- Ejection fraction (EF) of at least >= 40% by multigated acquisition (MUGA) or echocardiography (ECHO)
- Total bilirubin =< 1.5 mg/dl
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 2.5 times the upper limit of normal without evidence of active infectious hepatitis
- Creatinine clearance >= 40 ml/min
- Platelets > 75,000 cells/ul
- Absolute neutrophil count (ANC) > 1,000 cells/ul
- Ability to provide informed consent
- Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) pregnancy test at screening; pregnancy testing is not required for: (a) women who have been post-menopausal for at least 2 years without menses; or (b) women who are surgically sterile (e.g. by means of hysterectomy, tubal ligation, etc.)
- Males and females of childbearing potential must be able and willing to use an effective contraceptive method during treatment and for three months after completing treatment
Who cannot join
- Active infections (bacterial, fungal, or viral)
- Evidence of sanctuary site involvement by disease, e.g., central nervous system, ocular, testicular involvement
- Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
- Recent chemotherapy within 3 weeks of screening
- Major surgery within 4 weeks of screening
- Diagnosed or treated for malignancy other than NHL for which patient will be treated, except: malignancy treated with curative intent and with no known active disease present for >= 3 years before subject registration; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease
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- History of stroke or intracranial hemorrhage within 6 months prior to registration
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists
- Requires treatment with strong cytochrome (CYP3A4/5) inhibitors
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
- Women who are pregnant or breastfeeding
- Prior use of brentuximab vedotin
- Prior use of bendamustine for indolent lymphoma allowed if > 2 years, CR to bendamustine and well tolerated with no residual > grade 1 toxicity; no prior use of bendamustine for aggressive lymphoma allowed
- Prior allogeneic transplant
- Patients with Child-Pugh B or C hepatic impairment
Trial locations and contacts
1 site in 1 country.
United States1 site
Arizona Cancer Center at UMC North
Tucson, Arizona, 85724
About this study
Official title: Phase II Study of Brentuximab Vedotin in Combination With Bendamustine and Rituximab, in Patients With CD30 Positive, Relapsed or Refractory B Cell Non-Hodgkin Lymphoma (NHL)
This phase II trial studies how well brentuximab vedotin, bendamustine, and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, use antibody to target chemotherapy in cancer cells. Drugs used in chemotherapy, such as bendamustine, work in different ways to kill cancer cells. Monoclonal antibodies, such as rituximab, kill the cancer cells directly, but also harness the immune system to kill the cancer cells. Adding brentuximab to rituximab may improve response rates in CD30 positive, CD20 positive Relapsed Refactory NHL.
Read the detailed description
PRIMARY OBJECTIVES:
- Complete response (CR) rate and overall response rate (ORR) for patients with relapsed aggressive high-risk non-Hodgkin lymphoma (NHL) treated with brentuximab vedotin, bendamustine and rituximab (S-BR).
SECONDARY OBJECTIVES:
- To estimate 2-year progression-free survival (PFS). II. To evaluate rate of positron emission tomography (PET)-CR and correlation to 2 year PFS.
III. To evaluate the toxicity of six cycles of S-BR. IV. To evaluate mobilization, stem cell collection, engraftment in patients that proceed to salvage autologous stem cell transplant (ASCT).
SCIENTIFIC OBJECTIVES:
- To evaluate percentage of tumor cells that are positive or negative for cluster of differentiation (CD)30 by immunohistochemistry (IHC), the subcellular location of CD30 (membrane or cytoplasmic only with absence of membrane expression), intensity of scoring, and correlating with clinical outcomes.
II. To evaluate gene expression profiling (GEP) by Nanostring Technology and comparing expression levels of target genes in CD30 membrane positive, CD30 cytoplasmic only positive or CD30 negative tumor cells.
III. To evaluate correlation between mutations identified through next generation sequencing (NGS) including ribonucleic acid (RNA) sequencing of the tumor transcriptome, and correlating to GEP and CD30 IHC, and correlating to clinical outcomes.
IV. To evaluate the levels of soluble CD30 at baseline and in response to treatment.
SCHEDULE:
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1, bendamustine IV over 30-60 minutes on days 1-2, and rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years.
- Conditions
- Diffuse Large B Cell Lymphoma, Mediastinal Large B-cell Lymphoma, Grey Zone Lymphoma, High Grade B Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- Being tested
- Brentuximab, Bendamustine, Rituximab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrentuximabDrug
Also called Brentuximab Vedotin, Adcetris
Brentuximab vedotin IV over 30 minutes on day 1.Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
BendamustineDrug
Also called Treanda
Bendamustine IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
RituximabDrug
Also called Rituxan
Rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Brentuximab, Bendamustine, Rituximab | Experimental | Brentuximab Vedotin in Combination with Bendamustine and Rituximab Receives: Drug: Brentuximab; Drug: Bendamustine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
CR rate
The complete response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Measured: Up to 2 years after completion of study treatment
Percentage of patients obtaining a CR + PR using Cheson criteria
The overall response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Measured: Up to 2 years after completion of study treatment
Secondary outcomes (7)
Median time to progression
Measured: At 2 years
PFS
PFS will be estimated using the Kaplan-Meier estimate, with stratification by allogeneic stem cell transplantation status.
Measured: At 2 years
Complete response rate assessed by PET/CT
The complete response rate by PET/CT will be estimated with the 95% exact confidence interval.
Measured: Up to 2 years after the completion of study treatment
Frequency of adverse events (AEs) and serious AEs assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
The proportion of patients with treatment-emergent AEs will be tabulated, including by causality, seriousness, severity/grade, and whether the AE resulted in death or discontinuation of treatment.
Measured: Up to 2 years after completion of study treatment
CD34+ peripheral blood stem cells assessed by flow cytometry
Only for subjects receiving transplant
Measured: Up to 2 years after completion of study treatment
Median time to engraftment
Only for subjects receiving transplant
Measured: Up to 2 years after completion of study treatment
Soluble CD30 levels in blood by biochemical assay
Brentuximab vedotin pharmacokinetics in combination therapy will be measured and correlated to single agent data.
Measured: 48-72 hours after brentuximab vedotin treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2015 (estimated)
- Study start16 Dec 2015
- Primary completion17 May 2017
- Study completion17 May 2017
Why it stopped: Pharmaceutical company supplying the drug withdraw financial support. PI has decided to close study prior to enrollment of any patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel O. Persky, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02623920
- Sponsor's protocol ID
- 1507953455
- Acronym
- S-BR
- Status last verified
- May 2017
- First submitted
- 24 Sep 2015
- Last updated
- 19 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Brentuximab Vedotin in Combination With Bendamustine and Rituximab, in Patients With CD30 Positive, Relapsed or Refractory B Cell Non-Hodgkin Lymphoma (NHL)
- ClinicalTrials.gov ID
- NCT02623920
- Acronym / sponsor ID
- S-BR / 1507953455
- Conditions
- Diffuse Large B Cell Lymphoma, Mediastinal Large B-cell Lymphoma, Grey Zone Lymphoma, High Grade B Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Pharmaceutical company supplying the drug withdraw financial support. PI has decided to close study prior to enrollment of any patients.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- 16 Dec 2015 (actual)
- Primary completion
- 17 May 2017 (actual)
- Study completion
- 17 May 2017 (actual)
- First posted
- 8 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well brentuximab vedotin, bendamustine, and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, use antibody to target chemotherapy in cancer cells. Drugs used in chemotherapy, such as bendamustine, work in different ways to kill cancer cells. Monoclonal antibodies, such as rituximab, kill the cancer cells directly, but also harness the immune system to kill the cancer cells. Adding brentuximab to rituximab may improve response rates in CD30 positive, CD20 positive Relapsed Refactory NHL.
Detailed description
PRIMARY OBJECTIVES:
- Complete response (CR) rate and overall response rate (ORR) for patients with relapsed aggressive high-risk non-Hodgkin lymphoma (NHL) treated with brentuximab vedotin, bendamustine and rituximab (S-BR).
SECONDARY OBJECTIVES:
- To estimate 2-year progression-free survival (PFS). II. To evaluate rate of positron emission tomography (PET)-CR and correlation to 2 year PFS.
III. To evaluate the toxicity of six cycles of S-BR. IV. To evaluate mobilization, stem cell collection, engraftment in patients that proceed to salvage autologous stem cell transplant (ASCT).
SCIENTIFIC OBJECTIVES:
- To evaluate percentage of tumor cells that are positive or negative for cluster of differentiation (CD)30 by immunohistochemistry (IHC), the subcellular location of CD30 (membrane or cytoplasmic only with absence of membrane expression), intensity of scoring, and correlating with clinical outcomes.
II. To evaluate gene expression profiling (GEP) by Nanostring Technology and comparing expression levels of target genes in CD30 membrane positive, CD30 cytoplasmic only positive or CD30 negative tumor cells.
III. To evaluate correlation between mutations identified through next generation sequencing (NGS) including ribonucleic acid (RNA) sequencing of the tumor transcriptome, and correlating to GEP and CD30 IHC, and correlating to clinical outcomes.
IV. To evaluate the levels of soluble CD30 at baseline and in response to treatment.
SCHEDULE:
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1, bendamustine IV over 30-60 minutes on days 1-2, and rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brentuximab, Bendamustine, Rituximab | Experimental | Drug: Brentuximab, Drug: Bendamustine, Drug: RituximabBrentuximab Vedotin in Combination with Bendamustine and Rituximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- CD30 detectable B lineage relapsed refractory NHL including the following histologies:
- Subjects between 18 and 75 years old. Subjects older than 75 years old to be discussed with PI prior to subject consent; consensus between PI and treating physician is required.
- Karnofsky performance status (KPS) >= 70%, Eastern Cooperative Oncology Group (ECOG) =< 2
- At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
- Patients must have received at least one but no more than 4 prior lines of systemic therapy
Key exclusion criteria (16 listed)
- Active infections (bacterial, fungal, or viral)
- Evidence of sanctuary site involvement by disease, e.g., central nervous system, ocular, testicular involvement
- Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
- Recent chemotherapy within 3 weeks of screening
- Major surgery within 4 weeks of screening
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 |
|---|---|---|
| BrentuximabAlso: Brentuximab Vedotin, AdcetrisBrentuximab vedotin IV over 30 minutes on day 1.Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug | Brentuximab, Bendamustine, Rituximab |
| BendamustineAlso: TreandaBendamustine IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug | Brentuximab, Bendamustine, Rituximab |
| RituximabAlso: RituxanRituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug | Brentuximab, Bendamustine, Rituximab |
Primary outcome
CR rate
Time frame: Up to 2 years after completion of study treatment
The complete response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Percentage of patients obtaining a CR + PR using Cheson criteria
Time frame: Up to 2 years after completion of study treatment
The overall response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
7 secondary outcomes
Median time to progression
Time frame: At 2 years
PFS
Time frame: At 2 years
Complete response rate assessed by PET/CT
Time frame: Up to 2 years after the completion of study treatment
Frequency of adverse events (AEs) and serious AEs assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Up to 2 years after completion of study treatment
CD34+ peripheral blood stem cells assessed by flow cytometry
Time frame: Up to 2 years after completion of study treatment
Median time to engraftment
Time frame: Up to 2 years after completion of study treatment
Soluble CD30 levels in blood by biochemical assay
Time frame: 48-72 hours after brentuximab vedotin treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2017.
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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.
Daniel O. Persky, MD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brentuximab, Bendamustine and Rituximab in people with Diffuse Large B Cell Lymphoma and Mediastinal Large B-cell Lymphoma, run by University of Arizona at 1 site 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 19 inclusion and 16 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: withdrawn, as of the sponsor's last update on 19 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
CR rate (time frame: Up to 2 years after completion of study treatment). 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 19 May 2017.