PCNSLPhase 2NCT03392714
Bendamustine-based Combination Therapy for PCNSL
A Phase 2 study testing R-B(O)AD in people with PCNSL, run by Chonnam National University Hospital at 1 site in South Korea.
Trial summary
This pilot study will i) evaluate the efficacy and the safety of bendamustine-based combination chemotherapy and ii) investigate the pharmacokinetics (PK)of bendamustine in plasma and CSF when given as salvage treatment for patients with relapsed or refractory primary central nervous system lymphoma (PCNSL). Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- PCNSL
- What is being tested?
- R-B(O)AD
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSouth Korea
- Study dates
- 20 Jan 2016to 20 Jan 2019
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PCNSL of diffuse large B-cell lymphoma (DLBCL) with a CNS lesion by tissue biopsy
- Age ≥ 19 years old
- Relapsed or refractory PCNSL after frontline combined chemotherapy or radiation
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1000/uL
- Platelets ≥ 100,000/uL
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- Total bilirubin ≤ 1.5 x ULN (upper limit of normal)
- Aspartate aminotransferase (AST) ≤ 3 x ULN
- Creatinine ≤ 2.0 x ULN
Who cannot join
- PCNSL of other than DLBCL or T-cell lymphoma with a CNS lesion by tissue biopsy
- Any of the following: pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception
- Uncontrolled infection
- Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration
- Persistent toxicities ≥ grade 3 from prior chemotherapy or biologic therapy regardless of interval since last treatment
- History of thromboembolic episodes ≤ 3 months prior to registration
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- Active hepatitis B or C with uncontrolled disease
- Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
- Any severe and/or uncontrolled medical conditions or other conditions that could adversely impact their ability to participate in the study
- Major surgery ≤ 4 weeks prior to registration or have not recovered from side effects of such therapy
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Chonnam National University Hwasun Hospital
Hwasun-gun, Jeollanam-do, 519-809
About this study
Official title: Plasma and Cerebrospinal Fluid (CSF) Pharmacokinetics of Bendamustine as a Component of Salvage Therapy for Primary Central Nervous System Lymphoma (PCNSL)
This pilot study will i) evaluate the efficacy and the safety of bendamustine-based combination chemotherapy and ii) investigate the pharmacokinetics (PK)of bendamustine in plasma and CSF when given as salvage treatment for patients with relapsed or refractory primary central nervous system lymphoma (PCNSL).
Read the detailed description
A relatively high proportion of patients diagnosed with primary CNS lymphoma will experience recurrent disease, yet therapy options are limited in salvage therapy. Based on the demonstrated activity and proposed additive mechanisms of the chemotherapeutic agents included in the bendamustine-based combination regimen, the efficacy and safety of R-B(O)AD will be evaluated for treatment of relapsed/refractory (R/R) primary CNS lymphoma. Evidence from previous preclinical tissue distribution studies and single agent intravenous drug therapy trials in CNS malignancies suggests that bendamustine penetrates brain and tumor tissue, however there are no clinical data available on the PK of bendamustine in the CSF. This study will evaluate the PK of plasma and CSF drug levels through a population based nonlinear mixed-effects model approach in a R/R PCNSL cohort with the goals to define the currently unknown PK profile of bendamustine in the CSF and to further characterize the relationship between plasma and CSF drug levels, and the influence of exposure on response to therapy.
- Conditions
- PCNSL
- Being tested
- R-B(O)AD
- Keywords
- Bendamustine, CSF, Pharmacokinetics, PCNSL, Salvage therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R-B(O)ADDrug
rituximab 375 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1, omitted in patients ≥70 years of age due to risk of neurotoxicity; bendamustine 75 mg/m2 over 1 h on days 2 and 3; cytarabine 1000 mg/m2 over 3 h on days 2-4; dexamethasone 20 mg on days 1-4, administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| R-B(O)AD | Experimental | Intravenous R-B(O)AD every 4 weeks for up to 4 cycles Receives: Drug: R-B(O)AD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
rate of complete or partial response (CR/PR)
Measured: 2 year
Secondary outcomes (5)
Toxicity based on NCI Common Terminology Criteria version 4.0
adverse event incidence of combination regimen
Measured: 2 year
Progression-free survival (PFS)
calculated from the time of study entry until progression, relapse, or death
Measured: 2 years
Overall survival (OS)
calculated from the time of study entry until death
Measured: 2 years
Maximum concentration [Cmax] of bendamustine in plasma and CSF
peak concentration of bendamustine after 1 hour IV infusion
Measured: 6 months
Area under the curve [AUC] of bendamustine in plasma and CSF
overall exposure of bendamustine after IV infusion
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2018
- Study start20 Jan 2016
- Primary completion20 Jan 2018 (estimated)
- Study completion20 Jan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PCNSLStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chonnam National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deok-Hwan Yang, Chonnam National University Hospital
- Investigators
- Deok-Hwan Yang, MD, Principal investigator, Chonnam National University Hwasun Hospital, Department of Hematology-Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03392714
- Sponsor's protocol ID
- CNUHH-2016-145
- Status last verified
- Jan 2018
- First submitted
- 6 Dec 2017
- Last updated
- 8 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kim T, Choi HY, Lee HS, Jung SH, Ahn JS, Kim HJ, Lee JJ, Yoo HD, Yang DH. Clinical response and pharmacokinetics of bendamustine as a component of salvage R-B(O)AD therapy for the treatment of primary central nervous system lymphoma (PCNSL). BMC Cancer. 2018 Jul 9;18(1):729. doi: 10.1186/s12885-018-4632-y.
PubMed 29986691
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma and Cerebrospinal Fluid (CSF) Pharmacokinetics of Bendamustine as a Component of Salvage Therapy for Primary Central Nervous System Lymphoma (PCNSL)
- ClinicalTrials.gov ID
- NCT03392714
- Acronym / sponsor ID
- CNUHH-2016-145
- Conditions
- PCNSL
- Keywords
- Bendamustine, CSF, Pharmacokinetics, PCNSL, Salvage therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Chonnam National University HospitalUniversity, hospital or other
- Study start
- 20 Jan 2016 (actual)
- Primary completion
- 20 Jan 2018 (estimated)
- Study completion
- 20 Jan 2019 (estimated)
- First posted
- 8 Jan 2018 (actual)
- 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 pilot study will i) evaluate the efficacy and the safety of bendamustine-based combination chemotherapy and ii) investigate the pharmacokinetics (PK)of bendamustine in plasma and CSF when given as salvage treatment for patients with relapsed or refractory primary central nervous system lymphoma (PCNSL).
Detailed description
A relatively high proportion of patients diagnosed with primary CNS lymphoma will experience recurrent disease, yet therapy options are limited in salvage therapy. Based on the demonstrated activity and proposed additive mechanisms of the chemotherapeutic agents included in the bendamustine-based combination regimen, the efficacy and safety of R-B(O)AD will be evaluated for treatment of relapsed/refractory (R/R) primary CNS lymphoma. Evidence from previous preclinical tissue distribution studies and single agent intravenous drug therapy trials in CNS malignancies suggests that bendamustine penetrates brain and tumor tissue, however there are no clinical data available on the PK of bendamustine in the CSF. This study will evaluate the PK of plasma and CSF drug levels through a population based nonlinear mixed-effects model approach in a R/R PCNSL cohort with the goals to define the currently unknown PK profile of bendamustine in the CSF and to further characterize the relationship between plasma and CSF drug levels, and the influence of exposure on response to therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R-B(O)AD | Experimental | Drug: R-B(O)ADIntravenous R-B(O)AD every 4 weeks for up to 4 cycles |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- PCNSL of diffuse large B-cell lymphoma (DLBCL) with a CNS lesion by tissue biopsy
- Age ≥ 19 years old
- Relapsed or refractory PCNSL after frontline combined chemotherapy or radiation
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1000/uL
Key exclusion criteria (10 listed)
- PCNSL of other than DLBCL or T-cell lymphoma with a CNS lesion by tissue biopsy
- Any of the following: pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception
- Uncontrolled infection
- Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration
- Persistent toxicities ≥ grade 3 from prior chemotherapy or biologic therapy regardless of interval since last treatment
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 |
|---|---|---|
| R-B(O)ADrituximab 375 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1, omitted in patients ≥70 years of age due to risk of neurotoxicity; bendamustine 75 mg/m2 over 1 h on days 2 and 3; cytarabine 1000 mg/m2 over 3 h on days 2-4; dexamethasone 20 mg on days 1-4, administered intravenously | Drug | R-B(O)AD |
Primary outcome
Overall response rate (ORR)
Time frame: 2 year
rate of complete or partial response (CR/PR)
5 secondary outcomes
Toxicity based on NCI Common Terminology Criteria version 4.0
Time frame: 2 year
Progression-free survival (PFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Maximum concentration [Cmax] of bendamustine in plasma and CSF
Time frame: 6 months
Area under the curve [AUC] of bendamustine in plasma and CSF
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2018.
- Derived from this study: PubMed 29986691Kim T, Choi HY, Lee HS, Jung SH, Ahn JS, Kim HJ, Lee JJ, Yoo HD, Yang DH. Clinical response and pharmacokinetics of bendamustine as a component of salvage R-B(O)AD therapy for the treatment of primary central nervous system lymphoma (PCNSL). BMC Cancer. 2018 Jul 9;18(1):729. doi: 10.1186/s12885-018-4632-y.
- 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.
Deok-Hwan Yang, MD principal investigator
Chonnam National University Hwasun Hospital, Department of Hematology-Oncology
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 R-B(O)AD in people with PCNSL, run by Chonnam National University Hospital at 1 site in South Korea.
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 9 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 8 Jan 2018. 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 South Korea. 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?
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?
Overall response rate (ORR) (time frame: 2 year). 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 NCT03392714, 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 8 Jan 2018.