Antibiotics-unresponsive MALT LymphomaPhase 2LCMALTNCT04604028
Lenalidomide and Low-dose Cyclophosphamide for MALT Lymphoma
A Phase 2 study testing Lenalidomide [Leavdo®] in people with Antibiotics-unresponsive MALT Lymphoma and Relapsed MALT Type Extranodal Marginal Zone B-Cell Lymphoma, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the overall response rate as well as dural time of tumor remission, and avoid alternative treatments, including… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antibiotics-unresponsive MALT Lymphoma, Relapsed MALT Type Extranodal Marginal Zone B-Cell Lymphoma, Refractory Extranodal Marginal Zone B-Cell Lymphoma (MALT)
- What is being tested?
- Lenalidomide [Leavdo®]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteTaiwan
- Study dates
- 10 Nov 2020to 31 Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically verified diagnosis of MALT lymphoma arising at any extranodal site
- Diseases of extranodal MALT lymphoma 2.1 It does not initially respond to antibiotics or 2.2 It is refractory to or in first or greater relapse after prior radiotherapy and/ or chemotherapy and/or immunotherapy
- Measurable or non-measurable lesions where the response is nevertheless evaluable by non-imaging means (e.g., gastric or bone marrow infiltrations)
- Ann Arbor Stage I-IV
- ECOG performance status of 0, 1 or 2
- Age ≥ 18 years
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- Life expectancy of at least 3 months
- Adequate haematological status: ANC (absolute neutrophil count [segmented + bands]) ≥1.0 x 109/L, platelet count ≥ 75 x 109/L , haemoglobin ≥8 g/dL.
- Adequate cardiac, renal and liver function tests (serum creatinine < 2.0 mg/dl, ALT or AST < 2.5 x upper limit of normal range, alkaline phosphatase < 2.5 x upper limit of normal range, serum bilirubin < 2.0 mg/dl)
- Patient must be willing and able to comply with the protocol for the entire study duration
- Female patients of childbearing potential must agree to use, and be able to comply with, effective contraception and agree to have medically supervised pregnancy tests prior to starting the study treatment and during therapy
- Male patients must agree to always use a condom during any sexual contact with females of reproductive potential and agree to not donate sperm while taking lenalidomide
- Patient must agree to abstain from donating blood while taking study drug therapy
- Patient must agree not to share study medication with another person and to return all unused study drug to the investigator
Who cannot join
- Lymphoma histology other than MALT lymphoma or MALT lymphoma with a diffuse large cell lymphoma ("high grade lymphoma") component
- Use of any investigational agent within 28 days prior to initiation of treatment
- History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix or carcinoma in situ of the breast within the last 5 years unless in complete remission since at least 3 years
- Dependency on red blood cell and/or platelet transfusions
- Evidence of central nervous system involvement
- A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
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- Severe peripheral polyneuropathy
- Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months and/or long QT-syndrome
- HIV seropositivity
- Presence of active opportunistic infections
- Pregnancy or lactation
- Uncontrolled diabetes mellitus
- Pre-existing thromboembolic conditions at study entry
- Known hypersensitivity to thalidomide or lenalidomide antibiotics
- History of intolerance or hypersensitivity to aspirin
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of Combination of Oral Lenalidomide and Low-dose Cyclophosphamide for Patients With Antibiotics-unresponsive Extranodal Marginal Zone B-cell Lymphoma
Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the overall response rate as well as dural time of tumor remission, and avoid alternative treatments, including radiotherapy or chemotherapy-related adverse effects in antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma. Therefore, in this proposal, the investigators will design a prospective phase II study to evaluate the treatment efficacies of combination of oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days) in patients with antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma.
Read the detailed description
[Background]: In addition to Helicobacter pylori-negative gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (named as MALT lymphoma) (Sci Rep. 2017;7(1):14333), the investigators recently demonstrated that first-line antibiotics treatments can cure around 50% patients with stage IE/IIE1 extragastric MALT lymphoma (2018 ESMO poster discussion). However, the optimal management for antibiotics-unresponsive MALT lymphomas is not clearly defined.
[Rationale]: The investigators previously reported that thalidomide resulted in an overall response rate (ORR, including complete remission [CR] and partial remission [PR]) of 50% in 10 patients with antibiotics-unresponsive or chemotherapy-resistant MALT lymphoma. Lenalidomide (an immunomodulatory derivatives [IMiDs] of thalidomide) exhibits anti-angiogenic and immunomodulatory effects and has been proved efficacies in the treatment of multiple myeloma (MM). In the previous phase II study, single agent of lenalidomide resulted in ORR of 61.1% in 18 patients with MALT lymphoma. In addition to kill lymphoma cells, single low-dose cyclophosphamide, is an option for restoring immune response in patients with advanced cancer. The investigators also showed that low-dose cyclophosphamide (50 mg daily for 21 days, every 28 days) alone resulted in the ORR of 44.4 % in 9 patients with antibiotics-unresponsive MALT lymphoma. Previous studies also demonstrated that the addition of low-dose cyclophosphamide can overcome lenalidomide resistance in patients with MM.
[Hypotheses]: Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the ORR rate as well as dural time of tumor remission, and avoid alternative treatments, including radiotherapy or chemotherapy-related adverse effects in antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma.
[Methods]: Therefore, in this proposal, the investigators will design a prospective phase II study to evaluate the treatment efficacies of combination of oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days) in patients with antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma. The primary endpoint of this current study is ORR, and the second endpoint is adverse effect. The investigators will enroll 21 patients with antibiotics-unresponsive, relapsed or refractory MALT lymphoma based on the Simon minimax two-stage design.
The translational studies, including predictive markers and immunological profiles (BAFF-related canonical and non-canonical NF-κB signaling molecules, and immune-related molecules markers) will be included in the second points. The investigators will further assess immune-related molecules of nucleated cells of whole blood using flow cytometry, and analyze serum BAFF and cytokines.
- Conditions
- Antibiotics-unresponsive MALT Lymphoma, Relapsed MALT Type Extranodal Marginal Zone B-Cell Lymphoma, Refractory Extranodal Marginal Zone B-Cell Lymphoma (MALT)
- Being tested
- Lenalidomide [Leavdo®]
- Keywords
- Marginal zone B-cell lymphoma, Low-dose Cyclophosphamide, Lenalidomide
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenalidomide [Leavdo®]Drug
Also called Low-dose cyclophosphamide
Complete remission and partial remission rate
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide and low-dose cyclophosphamide | Experimental | Oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days Receives: Drug: Lenalidomide [Leavdo®] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor response rate
Included complete remission [CR] and partial remission [PR]
Measured: 1 year
Secondary outcomes (2)
Adverse Events assessments
Treatment-emergent adverse events (AEs) incidence, severity and relationship to study. treatment
Measured: 1 year
Biomakers
Predict the response of combination of lenalidomide and cyclophosphamide
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2020
- Study start10 Nov 2020 (estimated)
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antibiotics-unresponsive MALT LymphomaStudies of the same condition, open and under way.
- More trials run by National Taiwan 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
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sung-Hsin Kuo, M.D.,Ph.D, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04604028
- Sponsor's protocol ID
- 202003096MIPC
- Acronym
- LCMALT
- Status last verified
- Sep 2020
- First submitted
- 21 Sep 2020
- Last updated
- 27 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Combination of Oral Lenalidomide and Low-dose Cyclophosphamide for Patients With Antibiotics-unresponsive Extranodal Marginal Zone B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT04604028
- Acronym / sponsor ID
- LCMALT / 202003096MIPC
- Conditions
- Antibiotics-unresponsive MALT Lymphoma, Relapsed MALT Type Extranodal Marginal Zone B-Cell Lymphoma, Refractory Extranodal Marginal Zone B-Cell Lymphoma (MALT)
- Keywords
- Marginal zone B-cell lymphoma, Low-dose Cyclophosphamide, Lenalidomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 10 Nov 2020 (estimated)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 27 Oct 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.
Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the overall response rate as well as dural time of tumor remission, and avoid alternative treatments, including radiotherapy or chemotherapy-related adverse effects in antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma. Therefore, in this proposal, the investigators will design a prospective phase II study to evaluate the treatment efficacies of combination of oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days) in patients with antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma.
Detailed description
[Background]: In addition to Helicobacter pylori-negative gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (named as MALT lymphoma) (Sci Rep. 2017;7(1):14333), the investigators recently demonstrated that first-line antibiotics treatments can cure around 50% patients with stage IE/IIE1 extragastric MALT lymphoma (2018 ESMO poster discussion). However, the optimal management for antibiotics-unresponsive MALT lymphomas is not clearly defined.
[Rationale]: The investigators previously reported that thalidomide resulted in an overall response rate (ORR, including complete remission [CR] and partial remission [PR]) of 50% in 10 patients with antibiotics-unresponsive or chemotherapy-resistant MALT lymphoma. Lenalidomide (an immunomodulatory derivatives [IMiDs] of thalidomide) exhibits anti-angiogenic and immunomodulatory effects and has been proved efficacies in the treatment of multiple myeloma (MM). In the previous phase II study, single agent of lenalidomide resulted in ORR of 61.1% in 18 patients with MALT lymphoma. In addition to kill lymphoma cells, single low-dose cyclophosphamide, is an option for restoring immune response in patients with advanced cancer. The investigators also showed that low-dose cyclophosphamide (50 mg daily for 21 days, every 28 days) alone resulted in the ORR of 44.4 % in 9 patients with antibiotics-unresponsive MALT lymphoma. Previous studies also demonstrated that the addition of low-dose cyclophosphamide can overcome lenalidomide resistance in patients with MM.
[Hypotheses]: Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the ORR rate as well as dural time of tumor remission, and avoid alternative treatments, including radiotherapy or chemotherapy-related adverse effects in antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma.
[Methods]: Therefore, in this proposal, the investigators will design a prospective phase II study to evaluate the treatment efficacies of combination of oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days) in patients with antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma. The primary endpoint of this current study is ORR, and the second endpoint is adverse effect. The investigators will enroll 21 patients with antibiotics-unresponsive, relapsed or refractory MALT lymphoma based on the Simon minimax two-stage design.
The translational studies, including predictive markers and immunological profiles (BAFF-related canonical and non-canonical NF-κB signaling molecules, and immune-related molecules markers) will be included in the second points. The investigators will further assess immune-related molecules of nucleated cells of whole blood using flow cytometry, and analyze serum BAFF and cytokines.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide and low-dose cyclophosphamide | Experimental | Drug: Lenalidomide [Leavdo®]Oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically verified diagnosis of MALT lymphoma arising at any extranodal site
- Diseases of extranodal MALT lymphoma 2.1 It does not initially respond to antibiotics or 2.2 It is refractory to or in first or greater relapse after prior radiotherapy and/ or chemotherapy and/or immunotherapy
- Measurable or non-measurable lesions where the response is nevertheless evaluable by non-imaging means (e.g., gastric or bone marrow infiltrations)
- Ann Arbor Stage I-IV
- ECOG performance status of 0, 1 or 2
Key exclusion criteria (15 listed)
- Lymphoma histology other than MALT lymphoma or MALT lymphoma with a diffuse large cell lymphoma ("high grade lymphoma") component
- Use of any investigational agent within 28 days prior to initiation of treatment
- History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix or carcinoma in situ of the breast within the last 5 years unless in complete remission since at least 3 years
- Dependency on red blood cell and/or platelet transfusions
- Evidence of central nervous system involvement
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 |
|---|---|---|
| Lenalidomide [Leavdo®]Also: Low-dose cyclophosphamideComplete remission and partial remission rate | Drug | Lenalidomide and low-dose cyclophosphamide |
Primary outcome
Tumor response rate
Time frame: 1 year
Included complete remission [CR] and partial remission [PR]
2 secondary outcomes
Adverse Events assessments
Time frame: 1 year
Biomakers
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2020.
- Individual participant dataSharing planned: No
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.
Sung-Hsin Kuo, M.D.,Ph.D principal investigator
National Taiwan University Hospital
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 Lenalidomide [Leavdo®] in people with Antibiotics-unresponsive MALT Lymphoma and Relapsed MALT Type Extranodal Marginal Zone B-Cell Lymphoma, run by National Taiwan University Hospital at 1 site in Taiwan.
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 14 inclusion and 15 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 27 Oct 2020. 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 Taiwan. 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?
Contact Sung-Hsin Kuo, M.D.,Ph.D (-886-2-23123456 ext. 67144, shkuo101@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor response rate (time frame: 1 year). 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 27 Oct 2020; AzTrials last refreshed its copy on 1 Nov 2026.