Lymphoma, B-CellPhase 2RIPPLENCT04246359
Rituximab and Pegylated Interferon α-2b in Patients With Indolent B-cell Lymphoma
A Phase 2 study testing Rituximab Biosimilar and Pegylated Interferon α-2b in people with Lymphoma, B-Cell, run by Huiqiang Huang at 1 site in China.
Trial summary
A phase 2 open label study to evaluate safety and activity of Rituximab(HLX01) in combination with Pegylated interferon α-2b in patients with newly diagnosed advanced indolent B-cell lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lymphoma, B-Cell
- What is being tested?
- Rituximab Biosimilar and Pegylated Interferon α-2b
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteChina
- Study dates
- 15 Jan 2020to 16 Jan 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
- 18 to 80 years of age, male or female;
- Patients with a diagnosis of indolent B-cell non-Hodgkin's lymphoma (iNHL),including following subtypes：follicular lymphoma (grade Ⅰ, Ⅱ), intra-nodal and extra-mucosa-associated lymph Tissue marginal zone lymphoma (MALT), spleen marginal zone B-cell lymphoma, lymph node marginal zone lymphoma(MZL), Lymphocele lymphoma (except macroglobulinemia), small lymphocytic lymphoma(SLL);
- Treatment naive, and Lugano stage III-IV;
- Life expectancy at least 12 months;
- At least one evaluable or measurable disease that meets the Lugano 2014 criteria for malignant lymphoma [Evaluable lesions: 18 fluorodeoxyglucose-positron emission tomography (18FDG/PET) examination showed increased local uptake of lymph nodes or extranodal nodes (higher than liver) and PET and /or Computed Tomography (CT) features consistent with lymphoma features; Measurable lesions: nodular lesions> 15mm in diameter or extranodal lesions> 10mm (if only one measurable lesion has previously received radiotherapy, evidence of radiographic progression after radiotherapy is required), and accompanied by 18FDG increased intake]. It is necessary to exclude cases where there is no measurable lesion and diffuse liver 18FDG uptake is increased;
- ECOG score 0-2;
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- Organs and bone marrow function normally (within 14 days prior to study drug use, without receiving blood transfusion, granulocyte colony-stimulating factors or other related medical support):
- Absolute value of neutrophils ≥1.0 × 109 / L;
- Platelets ≥50 × 109 / L;
- Hemoglobin ≥8 g / dL;
- Serum creatinine ≤ 1.5 times Upper Limit Normal (ULN), or creatinine removal rate ≥40mL / min (estimated according to Cockcroft-Gault formula);
- serum total bilirubin ≤ 1.5 times ULN;
- Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) ≤ 2.5 times ULN;
- Coagulation function: International Normalized Ratio (INR)≤1.5 times ULN; Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤1.5 times ULN (unless the patient is receiving anticoagulant therapy and PT and APTT are within the expected range at the time of screening);
- Female patients of childbearing age must have a negative pregnancy test at the time of enrollment and are willing to use reliable contraceptive methods, i.e. barrier methods, oral contraceptives, implant methods, skin contraception, long-acting injection contraceptives, intrauterine devices, or tubal ligation;
- Sign the informed consent.
Who cannot join
- Primary CNS lymphoma or secondary CNS involvement;
- A history of severe allergic reactions to humanized or murine monoclonal antibodies;
- Patients have active autoimmune disease that requires systemic treatment in the past two years. (hormonal replacement therapy is not considered as a systemic treatment, such as patients with type 1 diabetes, adrenal function due to hypothyroidism that only requires thyroxine replacement therapy, low or pituitary dysfunction which only requires physiological doses of glucocorticoid replacement therapy); Patients with autoimmune disease without systemic treatment in the past two years can be enrolled;
- Patients who require systemic glucocorticoid therapy or other immunosuppressive therapy within 14 days before study 【patients are permitted to use topical, ocular, intra-articular, intranasal, and inhaled corticosteroids (with very low systemic absorption), to receive short-term (≤ 7 days) preventive treatment with glucocorticoids (such as contrast agent hypersensitivity) or treatment of non-autoimmune diseases (such as delayed onset of hypersensitivity caused by contact allergen】.Low-dose hormone debulking treatment due to large tumor burden is allowed (prednisone 20mg × 7 days or equivalent dose of other hormones are allowed);
- Have other malignancies in the past 5 years, except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the breast and carcinoma in situ of the cervix after radical treatment;
- Within 28 days before study treatment, patients receiving systemic anti-tumor treatments, including chemotherapy, immunotherapy, biotherapy (tumor vaccine, cytokine, or growth factor that controls cancer);
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- Major surgery was performed within 28 days before study treatment, or radiotherapy was performed within the first 90 days;
- Within 7 days before study treatment, patients receiving anti-cancer Chinese herbal medicine or proprietary Chinese medicine treatment;
- Live vaccines (excluding influenza attenuated vaccines) within 28 days before study treatment;
- A history of Human Immunodeficiency Virus (HIV) disease Patients with viral infection and / or acquired immunodeficiency syndrome;
- Patients with active chronic hepatitis B or active hepatitis C. Patients who are Hepatitis B Surface Antigen (HBsAg) or Hepatitis C Virus (HCV) antibodies positive during the screening period must have the Hepatitis B Virus (HBV) DNA titer test (must not higher than 2500 copies/mL or 1000 I /mL) and HCV RNA test (not to exceed the detection limit of the assay 10,000 copies/mL). Patients can enter the study if there is no treatment require. Patients with carriers of hepatitis B virus, stable hepatitis B after treatment (DNA titers of no more than 2500 copies / mL or 1000 IU / mL), and cured hepatitis C can be enrolled;
- Any active infection requiring systemic anti-infective treatment within 14 days study treatment;
- Female patients during pregnancy or lactation;
- Patients with a history of alcohol or drug abuse;
- Suffering from uncontrollable comorbidities, including but not limited to symptomatic congestive heart failure, uncontrollable hypertension, unstable angina pectoris, active peptic ulcer or bleeding disorders;
- A history of interstitial lung disease or non-infectious pneumonia. Patients who previously had drug-induced or radioactive non-infectious pneumonia but were asymptomatic were admitted;
- Patients with a history of mental illness, inability or restricted ability;
- On the judgement of the investigator, patient's underlying condition may increase his or her risk when receiving study medications or confuse the occurrence of a toxic reaction and its judgment；
- Patients of considered by investigators unsuitable for this study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Medical Oncology, Sun Yat-sen University Cancer Center,
Guangzhou, Guangdong, 510060
HuiQiang Huang, 86-020-87343350, huanghq@sysucc.org.cn
About this study
Official title: Safety and Activity of Rituximab(HLX01) in Combination With Pegylated Interferon α-2b in Patients With Newly Diagnosed Advanced Indolent B-cell Lymphoma: a Single-arm, Multicenter, Phase 2 Study
A phase 2 open label study to evaluate safety and activity of Rituximab(HLX01) in combination with Pegylated interferon α-2b in patients with newly diagnosed advanced indolent B-cell lymphoma.
Read the detailed description
Indolent B-cell lymphomas (iBCL), including follicular lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL, including Waldenström macroglobulinemia), and some cases of mantle cell lymphoma (MCL), disproportionally affect older individuals.Treatment options are heterogeneous, varying from watchful waiting to intensive combination therapy. Historically, rituximab based regimens have been used as standard immunochemotherapy for iBCL.Use of immunotherapy for indolent lymphoma had been advocated for many years and several studies reported benefit with interferon (IFN) in combination with chemotherapy or rituximab. The positive rate of HBsAg in B-cell NHL is about 30% in China.Pegylated interferon contribute to convert HBsAg to negative. We aim to evaluate safety and activity of Rituximab(HLX01) in combination with Pegylated interferon α-2b in patients with newly diagnosed advanced iBCL and HBsAg clearance rate of hepatitis B patients.
- Conditions
- Lymphoma, B-Cell
- Being tested
- Rituximab Biosimilar, Pegylated Interferon α-2b
- Keywords
- indolent B-cell lymphoma, Rituximab(HLX01), Pegylated Interferon α-2b, HBsAg clearance rate
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab BiosimilarDrug
Also called HLX01
To evaluate the short-term objective efficacy of HLX01 combined with Pegylated Interferon α-2b in patients with advanced idolent B-cell lymphoma.
Pegylated Interferon α-2bDrug
To evaluate the short-term objective efficacy of HLX01 combined with Pegylated Interferon α-2b in patients with advanced idolent B-cell lymphoma.
| Study group | Role | What they receive |
|---|---|---|
| RP induction and maintenance | Experimental | 1. Induction phase:
1. Rituximab: 375mg / m2, ivd, d1;
2. Pegylated interferon α-2b: 135 μg (500,000 U), H, d1, 8 Repeated every 21 days, Maximum 6 cycles 2. Maintenance phase:
1) Rituximab: 375mg / m2, ivd, d1; 2) Pegylated interferon α-2b: 135 μg (500,000 U), H, d1,30 Repeated every 2 months, Maximum 12 cycles Receives: Drug: Rituximab Biosimilar; Drug: Pegylated Interferon α-2b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)、Complete Remission Rate (CRR)、Partial Remission Rate (PRR)
Short-term effcacy according to Lugano 2014 Malignant Lymphoma Evaluation Criteria
Measured: Up to 21 weeks
HBsAg clearance rate and anti-Hbs antibody positive rate in patients with chronic hepatitis B at 72 weeks
Evaluate HBsAg clearance rate and positive rate of anti-Hbs antibody
Measured: Up to 72 weeks
Secondary outcomes (5)
Progression Free Survival (PFS) time,
PFS is defined as the time from the treatment date to the date of disease
Measured: Up to 3 years
Duration of Response (DOR)
Evaluate long-term survival time
Measured: Up to 3 years
Overall survival(OS)
Evaluate long-term survival time
Measured: Up to 5 years
Frequency and severity of adverse events (AE), frequency of Serious Adverse Event (SAE)
Incidence and Severity of Toxicities
Measured: Up to 2 years
Ratio of Physical Function and Fatigue Improvement by EORTC Quality of Life Scale QLQ-C30 (V3.0) (on the first day of each course and at each follow-up, up to 60 months)
Quality of Life evaluation to end of study
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2020
- Study start15 Jan 2020
- Primary completion16 Jun 2022 (estimated)
- Study completion16 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoma, B-CellStudies 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
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huiqiang Huang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Huiqiang Huang, Sun Yat-sen University
- Investigators
- Ye Cao, Professor, Principal investigator, Ethics Committee of Cancer Center of Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04246359
- Sponsor's protocol ID
- RIPPLE
- Acronym
- RIPPLE
- Status last verified
- Apr 2022
- First submitted
- 14 Jan 2020
- Last updated
- 7 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Activity of Rituximab(HLX01) in Combination With Pegylated Interferon α-2b in Patients With Newly Diagnosed Advanced Indolent B-cell Lymphoma: a Single-arm, Multicenter, Phase 2 Study
- ClinicalTrials.gov ID
- NCT04246359
- Acronym / sponsor ID
- RIPPLE / RIPPLE
- Conditions
- Lymphoma, B-Cell
- Keywords
- indolent B-cell lymphoma, Rituximab(HLX01), Pegylated Interferon α-2b, HBsAg clearance rate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Huiqiang HuangUniversity, hospital or other
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 16 Jun 2022 (estimated)
- Study completion
- 16 Jan 2023 (estimated)
- First posted
- 29 Jan 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.
A phase 2 open label study to evaluate safety and activity of Rituximab(HLX01) in combination with Pegylated interferon α-2b in patients with newly diagnosed advanced indolent B-cell lymphoma.
Detailed description
Indolent B-cell lymphomas (iBCL), including follicular lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL, including Waldenström macroglobulinemia), and some cases of mantle cell lymphoma (MCL), disproportionally affect older individuals.Treatment options are heterogeneous, varying from watchful waiting to intensive combination therapy. Historically, rituximab based regimens have been used as standard immunochemotherapy for iBCL.Use of immunotherapy for indolent lymphoma had been advocated for many years and several studies reported benefit with interferon (IFN) in combination with chemotherapy or rituximab. The positive rate of HBsAg in B-cell NHL is about 30% in China.Pegylated interferon contribute to convert HBsAg to negative. We aim to evaluate safety and activity of Rituximab(HLX01) in combination with Pegylated interferon α-2b in patients with newly diagnosed advanced iBCL and HBsAg clearance rate of hepatitis B patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RP induction and maintenance | Experimental | Drug: Rituximab Biosimilar, Drug: Pegylated Interferon α-2b1. Induction phase: 1. Rituximab: 375mg / m2, ivd, d1; 2. Pegylated interferon α-2b: 135 μg (500,000 U), H, d1, 8 Repeated every 21 days, Maximum 6 cycles 2. Maintenance phase: 1) Rituximab: 375mg / m2, ivd, d1; 2) Pegylated interferon α-2b: 135 μg (500,000 U), H, d1,30 Repeated every 2 months, Maximum 12 cycles |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 18 to 80 years of age, male or female;
- Patients with a diagnosis of indolent B-cell non-Hodgkin's lymphoma (iNHL),including following subtypes：follicular lymphoma (grade Ⅰ, Ⅱ), intra-nodal and extra-mucosa-associated lymph Tissue marginal zone lymphoma (MALT), spleen marginal zone B-cell lymphoma, lymph node marginal zone lymphoma(MZL), Lymphocele lymphoma (except macroglobulinemia), small lymphocytic lymphoma(SLL);
- Treatment naive, and Lugano stage III-IV;
- Life expectancy at least 12 months;
- At least one evaluable or measurable disease that meets the Lugano 2014 criteria for malignant lymphoma [Evaluable lesions: 18 fluorodeoxyglucose-positron emission tomography (18FDG/PET) examination showed increased local uptake of lymph nodes or extranodal nodes (higher than liver) and PET and /or Computed Tomography (CT) features consistent with lymphoma features; Measurable lesions: nodular lesions> 15mm in diameter or extranodal lesions> 10mm (if only one measurable lesion has previously received radiotherapy, evidence of radiographic progression after radiotherapy is required), and accompanied by 18FDG increased intake]. It is necessary to exclude cases where there is no measurable lesion and diffuse liver 18FDG uptake is increased;
Key exclusion criteria (19 listed)
- Primary CNS lymphoma or secondary CNS involvement;
- A history of severe allergic reactions to humanized or murine monoclonal antibodies;
- Patients have active autoimmune disease that requires systemic treatment in the past two years. (hormonal replacement therapy is not considered as a systemic treatment, such as patients with type 1 diabetes, adrenal function due to hypothyroidism that only requires thyroxine replacement therapy, low or pituitary dysfunction which only requires physiological doses of glucocorticoid replacement therapy); Patients with autoimmune disease without systemic treatment in the past two years can be enrolled;
- Patients who require systemic glucocorticoid therapy or other immunosuppressive therapy within 14 days before study 【patients are permitted to use topical, ocular, intra-articular, intranasal, and inhaled corticosteroids (with very low systemic absorption), to receive short-term (≤ 7 days) preventive treatment with glucocorticoids (such as contrast agent hypersensitivity) or treatment of non-autoimmune diseases (such as delayed onset of hypersensitivity caused by contact allergen】.Low-dose hormone debulking treatment due to large tumor burden is allowed (prednisone 20mg × 7 days or equivalent dose of other hormones are allowed);
- Have other malignancies in the past 5 years, except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the breast and carcinoma in situ of the cervix after radical 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 |
|---|---|---|
| Rituximab BiosimilarAlso: HLX01To evaluate the short-term objective efficacy of HLX01 combined with Pegylated Interferon α-2b in patients with advanced idolent B-cell lymphoma. | Drug | RP induction and maintenance |
| Pegylated Interferon α-2bTo evaluate the short-term objective efficacy of HLX01 combined with Pegylated Interferon α-2b in patients with advanced idolent B-cell lymphoma. | Drug | RP induction and maintenance |
Primary outcome
Objective Response Rate (ORR)、Complete Remission Rate (CRR)、Partial Remission Rate (PRR)
Time frame: Up to 21 weeks
Short-term effcacy according to Lugano 2014 Malignant Lymphoma Evaluation Criteria
HBsAg clearance rate and anti-Hbs antibody positive rate in patients with chronic hepatitis B at 72 weeks
Time frame: Up to 72 weeks
Evaluate HBsAg clearance rate and positive rate of anti-Hbs antibody
5 secondary outcomes
Progression Free Survival (PFS) time,
Time frame: Up to 3 years
Duration of Response (DOR)
Time frame: Up to 3 years
Overall survival(OS)
Time frame: Up to 5 years
Frequency and severity of adverse events (AE), frequency of Serious Adverse Event (SAE)
Time frame: Up to 2 years
Ratio of Physical Function and Fatigue Improvement by EORTC Quality of Life Scale QLQ-C30 (V3.0) (on the first day of each course and at each follow-up, up to 60 months)
Time frame: Up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
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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.
Ye Cao, Professor principal investigator
Ethics Committee of Cancer Center of Sun Yat-sen University
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 Rituximab Biosimilar and Pegylated Interferon α-2b in people with Lymphoma, B-Cell, run by Huiqiang Huang at 1 site in China.
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 16 inclusion and 19 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 7 Apr 2022. 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 China. 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 Huiqiang Huang, Professor (+86 020 87343350, huanghq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR)、Complete Remission Rate (CRR)、Partial Remission Rate (PRR) (time frame: Up to 21 weeks). 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 7 Apr 2022.