Central Nervous System LymphomaPhase 2C-R-HDMTXNCT04516655
A Phase II Trail of Chidamide ,Rituximab and Methotrexate in Lymphoma Patients
A Phase 2 study testing chidamide combined with rituximab and high-dose methotrexate in people with Central Nervous System Lymphoma, run by Fudan University.
Trial summary
This study will evaluate the efficacy, safety and patient reported outcomes of chidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles in untreated patients with primary central nervous system lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Central Nervous System Lymphoma
- What is being tested?
- chidamide combined with rituximab and high-dose methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2020to 30 Aug 2023
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ECOG Performance Status of 0, 1, or 2
- Previously untreated patients with primary central nervous system lymphoma with pathologically confirm
- At least one bi-dimensionally measurable lesion, defined as >1.0 cm in its longest dimension as measured by MRI
- Signed written Informed Consent Form
- hematologic function,defined as follows:
- Hemoglobin ³ 9.0 g/dL without packed RBC transfusion during 14 days before first treatment
Show all 10Show fewer
- ANC ³ 1,000/µL
- Platelet count ³ 80,000/µL
- Adequate liver and kidney function function,defined as follows:
- Serum AST and ALT≤ 2.5 ULN ，Total bilirubin ≤ 1.5 ULN Serum creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula)
Who cannot join
- Evidence of extracranial involvement (such as testis and breast) and secondary CNS involvement
- Evidence of pleural fluid, ascites and pericardial effusion
- History or presence of prolonged QTc interval in ECG, QTc interval>470ms in female and >450ms in male
- History of other malignancy in 5 years
- Positive test results for hepatitis C, HIV and RPR.
- Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology) Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) DNA is less than 10E4 at the time of screening.
Show all 10Show fewer
- Pregnancy or lactation or intending to become pregnant during study
- Prior organ transplantation
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or significant infections within 2 weeks before the start of Cycle 1.
- Evidence of significant, uncontrolled, epilepsy
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase II， Single-arm Trail of Chidamide Combined With Rituximab and High-dose Methotrexate in Previously Untreated Patients With Primary Central Nervous System Lymphoma
This study will evaluate the efficacy, safety and patient reported outcomes of chidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles in untreated patients with primary central nervous system lymphoma.
The primary study endpoint will be complete response (CR) rate as assessed by the investigator. The hypothesis is previously untreated patients with primary central nervous system lymphoma could achieve a CR rate of 80% with C-R-HDMTX.
- Conditions
- Central Nervous System Lymphoma
- Being tested
- chidamide combined with rituximab and high-dose methotrexate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
chidamide combined with rituximab and high-dose methotrexateDrug
chidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles in untreated patients with primary central nervous system lymphoma
| Study group | Role | What they receive |
|---|---|---|
| C-R-MTX | Experimental | chidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles Receives: Drug: chidamide combined with rituximab and high-dose methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
CR rate
CR rate of the lesion of previously untreated patients with primary central nervous system lymphoma according to the international collaborative evaluation criteria for central nervous system lymphoma （2005）with Enhanced MRI every 2 cycles
Measured: up to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2020
- Study start1 Sep 2020 (estimated)
- Primary completion1 Sep 2021 (estimated)
- Study completion30 Aug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fangfang Lv, MD, Fudan University
- Investigators
- Fangfang Lv, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04516655
- Sponsor's protocol ID
- C-R-HDMTX
- Acronym
- C-R-HDMTX
- Status last verified
- Aug 2020
- First submitted
- 11 Aug 2020
- Last updated
- 18 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gerstner ER, Batchelor TT. Primary central nervous system lymphoma. Arch Neurol. 2010 Mar;67(3):291-7. doi: 10.1001/archneurol.2010.3.
PubMed 20212226Batchelor TT. Primary central nervous system lymphoma: A curable disease. Hematol Oncol. 2019 Jun;37 Suppl 1:15-18. doi: 10.1002/hon.2598.
PubMed 31187523Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003 Mar 15;21(6):1044-9. doi: 10.1200/JCO.2003.03.036.
PubMed 12637469Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010 Jul;12(7):736-44. doi: 10.1093/neuonc/noq011. Epub 2010 Feb 8.
PubMed 20511181DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002 Dec 15;20(24):4643-8. doi: 10.1200/JCO.2002.11.013.
PubMed 12488408Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. doi: 10.1200/JCO.2006.06.6910.
PubMed 17008697Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007 Oct 20;25(30):4730-5. doi: 10.1200/JCO.2007.12.5062.
PubMed 17947720Wieduwilt MJ, Valles F, Issa S, Behler CM, Hwang J, McDermott M, Treseler P, O'Brien J, Shuman MA, Cha S, Damon LE, Rubenstein JL. Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res. 2012 Feb 15;18(4):1146-55. doi: 10.1158/1078-0432.CCR-11-0625. Epub 2012 Jan 6.
PubMed 22228634Gregory G, Arumugaswamy A, Leung T, Chan KL, Abikhair M, Tam C, Bajel A, Cher L, Grigg A, Ritchie D, Opat S. Rituximab is associated with improved survival for aggressive B cell CNS lymphoma. Neuro Oncol. 2013 Aug;15(8):1068-73. doi: 10.1093/neuonc/not032. Epub 2013 Mar 15.
PubMed 23502429Holdhoff M, Ambady P, Abdelaziz A, Sarai G, Bonekamp D, Blakeley J, Grossman SA, Ye X. High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma. Neurology. 2014 Jul 15;83(3):235-9. doi: 10.1212/WNL.0000000000000593. Epub 2014 Jun 13.
PubMed 24928128Ly KI, Crew LL, Graham CA, Mrugala MM. Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience. Oncol Lett. 2016 May;11(5):3471-3476. doi: 10.3892/ol.2016.4393. Epub 2016 Mar 30.
PubMed 27123138Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. doi: 10.1182/blood-2014-10-604561. Epub 2015 Jan 7.
PubMed 25568347Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. doi: 10.1200/JCO.2015.64.8634. Epub 2016 Mar 28.
PubMed 27022122Song Y, Wen Y, Xue W, Zhang Y, Zhang M. Effect of rituximab on primary central nervous system lymphoma: a meta-analysis. Int J Hematol. 2017 Nov;106(5):612-621. doi: 10.1007/s12185-017-2316-z. Epub 2017 Sep 12.
PubMed 28900847Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31;374(9700):1512-20. doi: 10.1016/S0140-6736(09)61416-1. Epub 2009 Sep 18.
PubMed 19767089
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II， Single-arm Trail of Chidamide Combined With Rituximab and High-dose Methotrexate in Previously Untreated Patients With Primary Central Nervous System Lymphoma
- ClinicalTrials.gov ID
- NCT04516655
- Acronym / sponsor ID
- C-R-HDMTX / C-R-HDMTX
- Conditions
- Central Nervous System Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Sep 2020 (estimated)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 30 Aug 2023 (estimated)
- First posted
- 18 Aug 2020 (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 study will evaluate the efficacy, safety and patient reported outcomes of chidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles in untreated patients with primary central nervous system lymphoma.
The primary study endpoint will be complete response (CR) rate as assessed by the investigator. The hypothesis is previously untreated patients with primary central nervous system lymphoma could achieve a CR rate of 80% with C-R-HDMTX.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| C-R-MTX | Experimental | Drug: chidamide combined with rituximab and high-dose methotrexatechidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ECOG Performance Status of 0, 1, or 2
- Previously untreated patients with primary central nervous system lymphoma with pathologically confirm
- At least one bi-dimensionally measurable lesion, defined as >1.0 cm in its longest dimension as measured by MRI
- Signed written Informed Consent Form
- hematologic function,defined as follows:
Key exclusion criteria (10 listed)
- Evidence of extracranial involvement (such as testis and breast) and secondary CNS involvement
- Evidence of pleural fluid, ascites and pericardial effusion
- History or presence of prolonged QTc interval in ECG, QTc interval>470ms in female and >450ms in male
- History of other malignancy in 5 years
- Positive test results for hepatitis C, HIV and RPR.
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 |
|---|---|---|
| chidamide combined with rituximab and high-dose methotrexatechidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles in untreated patients with primary central nervous system lymphoma | Drug | C-R-MTX |
Primary outcome
CR rate
Time frame: up to 18 weeks
CR rate of the lesion of previously untreated patients with primary central nervous system lymphoma according to the international collaborative evaluation criteria for central nervous system lymphoma （2005）with Enhanced MRI every 2 cycles
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2020.
- Results publication: PubMed 20212226Gerstner ER, Batchelor TT. Primary central nervous system lymphoma. Arch Neurol. 2010 Mar;67(3):291-7. doi: 10.1001/archneurol.2010.3.
- Results publication: PubMed 31187523Batchelor TT. Primary central nervous system lymphoma: A curable disease. Hematol Oncol. 2019 Jun;37 Suppl 1:15-18. doi: 10.1002/hon.2598.
- Results publication: PubMed 12637469Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003 Mar 15;21(6):1044-9. doi: 10.1200/JCO.2003.03.036.
- Results publication: PubMed 20511181Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010 Jul;12(7):736-44. doi: 10.1093/neuonc/noq011. Epub 2010 Feb 8.
- Results publication: PubMed 12488408DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002 Dec 15;20(24):4643-8. doi: 10.1200/JCO.2002.11.013.
- Results publication: PubMed 17008697Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. doi: 10.1200/JCO.2006.06.6910.
- Results publication: PubMed 17947720Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007 Oct 20;25(30):4730-5. doi: 10.1200/JCO.2007.12.5062.
- Results publication: PubMed 22228634Wieduwilt MJ, Valles F, Issa S, Behler CM, Hwang J, McDermott M, Treseler P, O'Brien J, Shuman MA, Cha S, Damon LE, Rubenstein JL. Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res. 2012 Feb 15;18(4):1146-55. doi: 10.1158/1078-0432.CCR-11-0625. Epub 2012 Jan 6.
- Results publication: PubMed 23502429Gregory G, Arumugaswamy A, Leung T, Chan KL, Abikhair M, Tam C, Bajel A, Cher L, Grigg A, Ritchie D, Opat S. Rituximab is associated with improved survival for aggressive B cell CNS lymphoma. Neuro Oncol. 2013 Aug;15(8):1068-73. doi: 10.1093/neuonc/not032. Epub 2013 Mar 15.
- Results publication: PubMed 24928128Holdhoff M, Ambady P, Abdelaziz A, Sarai G, Bonekamp D, Blakeley J, Grossman SA, Ye X. High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma. Neurology. 2014 Jul 15;83(3):235-9. doi: 10.1212/WNL.0000000000000593. Epub 2014 Jun 13.
- Results publication: PubMed 27123138Ly KI, Crew LL, Graham CA, Mrugala MM. Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience. Oncol Lett. 2016 May;11(5):3471-3476. doi: 10.3892/ol.2016.4393. Epub 2016 Mar 30.
- Results publication: PubMed 25568347Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. doi: 10.1182/blood-2014-10-604561. Epub 2015 Jan 7.
- 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.
Fangfang Lv principal investigator
Fudan University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing chidamide combined with rituximab and high-dose methotrexate in people with Central Nervous System Lymphoma, run by Fudan University.
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 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 18 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact Fangfang Lv (+86-18018312613, lvff80@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CR rate (time frame: up to 18 weeks). 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 NCT04516655, which also lists 25 linked publications.
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 18 Aug 2020.