Central Nervous System LymphomaPhase 2NCT06625359
High-dose Chemotherapy with Thiotepa, Busulfan, and Cyclophosphamide Followed by Autologous Stem Cell Transplantation in Central Nervous System Lymphoma
A Phase 2 study testing Thiotepa in conditioning before transplantation in people with Central Nervous System Lymphoma, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
The involvement of the central nervous system (CNS) by non-Hodgkin lymphoma (NHL) has carried a poor prognosis. For both of primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), high-dose methotrexate (HD- MTX) based chemotherapy and combined modality have significantly… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Central Nervous System Lymphoma
- What is being tested?
- Thiotepa in conditioning before transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Jun 2015to 30 Sep 2024
- 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
- ∙Patients with histologically confirmed primary central nervous system lymphoma or secondary CNS lymphoma defined as either synchronous CNS involvement of sys- temic NHL or as a site of recurrence in a patient s with a history of systemic NHL
- Patients who achieved remission after first line chemotherapy and/or WBRT, or who experience relapse of PCNSL/SCNLS.
- Patients who have not previously received therapy with high high-dose chemotherapy and stem cell transplantatitransplantation.
- The performance st atus of the patients should be 2 or less by ECOG performance scale.
- Patients should not have major illness or organ failure incompatible with autologous stem cell transplantation.
- Patients must have adequate hepatic function (serum bilirubin less than 2.0mg/dl, AST and ALT less than three times the upper normal limit)
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- Patients must have adequate renal function ( serum creatinin less than 2.0mg/dl)
- Patients must have adequate cardiac function (ejection fraction 45% on echo- cardiogram)
- Patients must have adequate bone marrow function (ANC 1,000/mm 3 and platelet count 75,000/mm 3 ∙ All patients are fully informed about the nature and purpose of this study and informed consent should be given before the start of treatment. All patients should fully understand the right or trial abandon without any disadvantage.
Who cannot join
- Concurrent history of neoplasm other than CNS lymphoma with life expectancy less than 3 months.
- History of clinically significant cardiac dysfunction (ex. CHF, symptomatic CAD, uncontrolled arrhythmia) or MI within 12 months.
- psychiatric disorders or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
- significant infection or uncontrolled bleeding
- enrollment of other clinical trials within 4 weeks prior to treatment
- any preexisting medical condition of sufficient severity to prevent full compliance with study
- patient being not willing to or unable to obey study protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of High-dose Chemotherapy with Thiotepa, Busulfan, and Cyclophosphamide Before Autologous Stem Cell Transplantation in Patients with Primary/secondary Central Nervous System Lymphoma
The involvement of the central nervous system (CNS) by non-Hodgkin lymphoma (NHL) has carried a poor prognosis. For both of primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), high-dose methotrexate (HD- MTX) based chemotherapy and combined modality have significantly improved the previously poor response rates and prognosis. However, in PCNSL, relapse rates have remained high, with only 20% to 30% patients achieving a durable long-term remission after HD-MTX. The combination with whole-brain radiotherapy (WBRT) has resulted in higher disease-free and overall survival rates, but it has also been associated with severe neurotoxicity. Patients with SCNSL fare the worst, typically succumbing to disease within median 2.5 to 4 months with 1-year survival rates of only 25%.
Because of these dismal outcomes, intensification of the high-dose chemotherapy (HDC)with autologous stem cell transplantation (autoSCT) has been explored for PCNSL and SCNSL as salvage treatment in patients with refractory or relapsed disease, and as consolidation after primary chemotherapy, replacing or preceding WBRT. Thiotepa, busulfan, and cyclophosphamide (TBC) have significant penetration of blood-brain barrier as shown in several pharmacokinetic studies. Thus, combination of these 3 agents was proposed as one high-dose chemotherapy regimen to achieve therapeutic concentrations in the lymphoma tissue in chemotherapy sanctuaries, like cerebrospinal fluid (CSF), meninges and eyes. eyes. Several studies have shown promising results and favorable long-term toxicity profiles with this combination. However, the relatively rarity of this tumor precludes rapid completion of large-scale phase III trial and, therefore, our reliance on the results of well-designed phase II trials is critical. Therefore, we evaluate the efficacy and toxicity of thiotepa, bulsulfan, and cyclophosphamide as a conditioning for autologous stem cell transplantation in patients with PCNSL and SCNSL.
- Conditions
- Central Nervous System Lymphoma
- Being tested
- Thiotepa in conditioning before transplantation
- Keywords
- PCNSL, SCNSL, high-dose chemotherapy followed by autoSCT, Thiotepa, Busulfan, Cyclophosphamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thiotepa in conditioning before transplantationDrug
Also called high-dose CTx with TBC, followed by auto-SCT
For patients with ECOG PS 0 or 1 For patients with ECOG PS 0 or 1 and age \< 60 years old, conditioning regimen before autologous stem cell transplantation consists of thiotepa, bulsulfan, and cyclophosphamide from day -9. Beginning on day -9 and through day -7, each patient was treated with thiotepa (200mg/m m2 IV per day). On days -6 to -4, patients received bulsulfan (2.7mg/kg IV over 3 hours per day every). Bulsulfan-related seizure prophylaxis was given with levetriacetam (1500mg loading on day -6, 500mg twice daily on days -5 to -3). On days -3 and -2, cyclophosphamide (60mg/kg IV per day) was given given.
Patients with ECOG PS 2 or age ≥ 60 years old received bulsulfan (3.2mg/kg IV over 3 hours per day for 2 days) resulting in 8 days regimen.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Patients with histologically confirmed primary central nervous system lymphoma or secondary CNS lymphoma defined as either synchronous CNS involvement of sys- temic NHL or as a site of recurrence in a patient s with a history of systemic NHL
* Patients who achieved remission after first line chemotherapy and/or WBRT, or who experience relapse of PCNSL/SCNLS.
* Patients who have not previously received therapy with high high-dose chemotherapy and stem cell transplantatitransplantation.
* The performance st atus of the patients should be 2 or less by ECOG performance scale.
* Patients should not have major illness or organ failure incompatible with autologous stem cell transplantation. Receives: Drug: Thiotepa in conditioning before transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
PFS was calculated from the date of transplantation to the date of disease progression or death from any cause. Patients who were alive without relapse or progression were censored at the time of last contact.
Measured: 1-year PFS
Secondary outcomes (4)
Overall survival (OS)
OS was calculated from the date of transplantation to death from any cause.
Measured: through study completion, an average of 1 year
Relapse rate
Measured: through study completion, an average of 1 year
Non-relapse mortality (NRM)
NRM was defined as any death without evidence of relapse.
Measured: through study completion, an average of 1 year
Toxicity profile
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2024
- Study start1 Jun 2015
- Primary completion30 Sep 2024
- Study completion30 Sep 2024
Why it stopped: slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, YOUNGIL KOH, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06625359
- Sponsor's protocol ID
- C-1503-129-659
- Status last verified
- Oct 2024
- First submitted
- 30 Sep 2024
- Last updated
- 3 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: not determined
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of High-dose Chemotherapy with Thiotepa, Busulfan, and Cyclophosphamide Before Autologous Stem Cell Transplantation in Patients with Primary/secondary Central Nervous System Lymphoma
- ClinicalTrials.gov ID
- NCT06625359
- Acronym / sponsor ID
- C-1503-129-659
- Conditions
- Central Nervous System Lymphoma
- Keywords
- PCNSL, SCNSL, high-dose chemotherapy followed by autoSCT, Thiotepa, Busulfan, Cyclophosphamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow enrollment
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 1 Jun 2015 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 30 Sep 2024 (actual)
- First posted
- 3 Oct 2024 (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.
The involvement of the central nervous system (CNS) by non-Hodgkin lymphoma (NHL) has carried a poor prognosis. For both of primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), high-dose methotrexate (HD- MTX) based chemotherapy and combined modality have significantly improved the previously poor response rates and prognosis. However, in PCNSL, relapse rates have remained high, with only 20% to 30% patients achieving a durable long-term remission after HD-MTX. The combination with whole-brain radiotherapy (WBRT) has resulted in higher disease-free and overall survival rates, but it has also been associated with severe neurotoxicity. Patients with SCNSL fare the worst, typically succumbing to disease within median 2.5 to 4 months with 1-year survival rates of only 25%.
Because of these dismal outcomes, intensification of the high-dose chemotherapy (HDC)with autologous stem cell transplantation (autoSCT) has been explored for PCNSL and SCNSL as salvage treatment in patients with refractory or relapsed disease, and as consolidation after primary chemotherapy, replacing or preceding WBRT. Thiotepa, busulfan, and cyclophosphamide (TBC) have significant penetration of blood-brain barrier as shown in several pharmacokinetic studies. Thus, combination of these 3 agents was proposed as one high-dose chemotherapy regimen to achieve therapeutic concentrations in the lymphoma tissue in chemotherapy sanctuaries, like cerebrospinal fluid (CSF), meninges and eyes. eyes. Several studies have shown promising results and favorable long-term toxicity profiles with this combination. However, the relatively rarity of this tumor precludes rapid completion of large-scale phase III trial and, therefore, our reliance on the results of well-designed phase II trials is critical. Therefore, we evaluate the efficacy and toxicity of thiotepa, bulsulfan, and cyclophosphamide as a conditioning for autologous stem cell transplantation in patients with PCNSL and SCNSL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Thiotepa in conditioning before transplantationPatients with histologically confirmed primary central nervous system lymphoma or secondary CNS lymphoma defined as either synchronous CNS involvement of sys- temic NHL or as a site of recurrence in a patient s with a history of systemic NHL * Patients who achieved remission after first line chemotherapy and/or WBRT, or who experience relapse of PCNSL/SCNLS. * Patients who have not previously received therapy with high high-dose chemotherapy and stem cell transplantatitransplantation. * The performance st atus of the patients should be 2 or less by ECOG performance scale. * Patients should not have major illness or organ failure incompatible with autologous stem cell transplantation. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ∙Patients with histologically confirmed primary central nervous system lymphoma or secondary CNS lymphoma defined as either synchronous CNS involvement of sys- temic NHL or as a site of recurrence in a patient s with a history of systemic NHL
- Patients must have adequate hepatic function (serum bilirubin less than 2.0mg/dl, AST and ALT less than three times the upper normal limit)
- Patients must have adequate renal function ( serum creatinin less than 2.0mg/dl)
- Patients must have adequate cardiac function (ejection fraction 45% on echo- cardiogram)
- Patients must have adequate bone marrow function (ANC 1,000/mm 3 and platelet count 75,000/mm 3 ∙ All patients are fully informed about the nature and purpose of this study and informed consent should be given before the start of treatment. All patients should fully understand the right or trial abandon without any disadvantage.
Key exclusion criteria (7 listed)
- Concurrent history of neoplasm other than CNS lymphoma with life expectancy less than 3 months.
- History of clinically significant cardiac dysfunction (ex. CHF, symptomatic CAD, uncontrolled arrhythmia) or MI within 12 months.
- psychiatric disorders or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
- significant infection or uncontrolled bleeding
- enrollment of other clinical trials within 4 weeks prior to 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 |
|---|---|---|
| Thiotepa in conditioning before transplantationAlso: high-dose CTx with TBC, followed by auto-SCTFor patients with ECOG PS 0 or 1 For patients with ECOG PS 0 or 1 and age \< 60 years old, conditioning regimen before autologous stem cell transplantation consists of thiotepa, bulsulfan, and cyclophosphamide from day -9. Beginning on day -9 and through day -7, each patient was treated with thiotepa (200mg/m m2 IV per day). On days -6 to -4, patients received bulsulfan (2.7mg/kg IV over 3 hours per day every). Bulsulfan-related seizure prophylaxis was given with levetriacetam (1500mg loading on day -6, 500mg twice daily on days -5 to -3). On days -3 and -2, cyclophosphamide (60mg/kg IV per day) was given given. Patients with ECOG PS 2 or age ≥ 60 years old received bulsulfan (3.2mg/kg IV over 3 hours per day for 2 days) resulting in 8 days regimen. | Drug | Treatment arm |
Primary outcome
Progression-free survival (PFS)
Time frame: 1-year PFS
PFS was calculated from the date of transplantation to the date of disease progression or death from any cause. Patients who were alive without relapse or progression were censored at the time of last contact.
4 secondary outcomes
Overall survival (OS)
Time frame: through study completion, an average of 1 year
Relapse rate
Time frame: through study completion, an average of 1 year
Non-relapse mortality (NRM)
Time frame: through study completion, an average of 1 year
Toxicity profile
Time frame: through study completion, an average of 1 year
Results and safety
The study was stopped early (reason given: slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2024.
- Individual participant dataSharing planned: Undecided. not determined
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Thiotepa in conditioning before transplantation in people with Central Nervous System Lymphoma, run by Seoul 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 7 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 3 Oct 2024. 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?
The study was stopped early (reason given: slow enrollment). 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?
Progression-free survival (PFS) (time frame: 1-year PFS). 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 3 Oct 2024.