Mantle Cell Lymphoma RecurrentPhase 1/2NCT01322776
Combination of Bortezomib, Fludarabine and Cyclophosphamide Treat Recurrent Mantle Cell Lymphoma
A Phase 1/2 study testing Combination of Bortezomib, Fludarabine and Cyclophosphamide in people with Mantle Cell Lymphoma Recurrent, run by Sun Yat-sen University at 1 site in China.
Trial summary
This is a multi-center, single arm, open-label, prospective IIS study, which will enroll 40 recurrent MCL patients.The aim is to evaluate the efficacy and safety of bortezomib, fludarabine and cyclophosphamide treatment and also analyze the relationship between NF-kB activity and efficacy of bortezomib treatment and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mantle Cell Lymphoma Recurrent
- What is being tested?
- Combination of Bortezomib, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Mar 2011to Oct 2013
- Phase
- Phase 1/2
- 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
- Male or female patients 18 years or older;
- Histologically confirmed MCL (Initial diagnosis in hospitals other than sites must be reconfirmed;
- Recurrent patients after first-line or second-line chemotherapy;
- At least including the following characteristic immunophenotype confirmed by immunohistochemistry: CD 20+, CD5+ and cyclin D1+;
- At least 1 measurable site of tumor（long diameter > 2.0 cm by physical examination or > 1.5cm on CT;
- No involvement of central nervous system;
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- ECOG performance status ≤ 2，life expectancy>6 months;
- Within 14 days before enrollment，WBC > 3×10^9/L，neutrophils > 1.5×10^9/L，platelets > 75×10^9/L;
- ALT ≤ 2 × upper limit of normal (ULN)，AST ≤ 2×ULN，total bilirubin ≤ 2×ULN，serum creatinine ≤ 1.5×ULN，calculated creatinine clearance > 50ml/min;
- Female patients must be post menopausal, surgically sterile, or practicing an effective method of birth control;
- Male patients must agree to use an acceptable method of contraception for the duration of the study;
- All patients must have signed an informed consent document indicating that they understand the purpose and procedures required for the study and are willing to participate in the study.
Who cannot join
- Peripheral neuropathy or neuropathic pain of grade 2 or worse according to CTC AE 3.0;
- Prior treatment with bortezomib;
- Diagnosed as a malignancy other than MCL（Patients with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded;
- Any experimental or anti-cancer therapy within 4 weeks before the first dose of study drug (including rituximab, alemtuzumab or unconjugated therapeutic antibodies, radiation therapy, etc.);
- Fludarabine resistance or intolerance，exposure to fludarabine within 6 months before screening；History of allergic reaction to compounds containing boron, mannitol, fludarabine or cyclophosphamide;
- Patients with known diagnosis of active systemic infection, HIV or active hepatitis B (carriers of hepatitis B are permitted to enter study);
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- Serious medical (e.g., cardiac failure [New York Heart Association: NYHA Class III or IV, or left ventricular ejection fraction: LVEF < 50%], active peptic ulceration, or uncontrolled diabetes mellitus) or psychiatric illness likely to interfere with participation in this clinical study;
- Pregnancy or lactation;
- Female or male patients of child-bearing potential who will not use adequate contraception during the course of the study;
- Other condition likely to interfere with participation in this clinical study.
Trial locations and contacts
1 site in 1 country.
Huiqiang Huang contact
China1 site, 1 recruiting
- Recruiting
SunYat-sen University Cancer Centre
Guangzhou, Guangdong
Huiqiang Huang, huanghq@sysucc.org.cn
Huiqiang Huang
About this study
Official title: Phase 1 and 2 Study of Combination Treatment of Bortezomib, Fludarabine and Cyclophosphamide in Patients With Recurrent Mantle Cell Lymphoma
This is a multi-center, single arm, open-label, prospective IIS study, which will enroll 40 recurrent MCL patients.The aim is to evaluate the efficacy and safety of bortezomib, fludarabine and cyclophosphamide treatment and also analyze the relationship between NF-kB activity and efficacy of bortezomib treatment and whether NF-kB activity can predict MCL progression.
Read the detailed description
This is a multi-center, single arm, open-label, prospective IIS study, which will enroll 40 recurrent MCL patients.The aim is to evaluate the efficacy and safety of bortezomib, fludarabine and cyclophosphamide treatment and also analyze the relationship between NF-kB activity and efficacy of bortezomib treatment and whether NF-kB activity can predict MCL progression.
This study consists of three phases: screening/baseline phase, treatment phase and follow-up phase after the end of treatment.
At screening/baseline phase, investigators obtain informed consent form, check the inclusion/exclusion criteria and then collect the following data: demographics, medical history data, vital signs, ECG, MRI/CT/B-ultrasound/X-ray examinations, physical examination, laboratory examinations, pregnancy test (only female) and bone marrow biopsy and aspiration. Pathological diagnosis of mantle cell lymphoma should be established by lymph node biopsy or other tumor histopathological examination and immunophenotyping. At the same time, ECOG-performance status, Fact/GOG-Ntx questionnaire and NF-κB activity will be assessed.
During treatment period, patients will be treated with bortezomib, fludarabine and cyclophosphamide in a 28-day cycle. Patients achieve complete response (CR) or partial response (PR) can receive up to six cycles of VF (C) treatment, while those continue stable disease (SD) will be stopped after 4-cycle treatment and those with progressive disease (PD) will also be stopped after 2-cycle treatment. Due to adverse events, patients may receive reductions or deviate from the intended dose and duration of VF (C) treatment. These adjustments must be in accordance with the regulations in the protocol about the dose and time adjustment.
Maximum tolerated dose (MTD) of cyclophosphamide will be determined in accordance with the standard "3+3" method, testing three dose levels, 150mg/m2, 200mg/m2 and 250mg/m2. Cyclophosphamide dose escalation test will be conducted in the first cycle, with every three patients in a group. Patients' enrollment will be competed among different sites, but further step should be taken only after the 3 patients in one group complete the first cycle, their efficacy and safety have been completely evaluated, and the notification of going to next step by a CRO company. Subjects involved in the cyclophosphamide dose escalation test will continue initial cyclophosphamide dose during the entire study, except for possible dose adjustment determined by investigators due to DLT. After ascertaining MTD, new patients will be administrated with cyclophosphamide at the MTD. According to the dose escalation diagram, up to 18 patients will be involved in dose escalation phase. Subjects who discontinue the treatment due to causes other than DLT in the first cycle should be replaced by new participants to enter dose escalation test. DLT is defined as: a grade 4 neutropenia lasting longer than 7 days, a grade 4 thrombocytopenia, a neutropenic fever, or a grade 3 or above non-hematological toxicity (except for nausea, vomiting and alopecia); a grade 3 or above nausea, vomiting or diarrhea is considered as DLT only if still observed after treatment. Please refer to dose escalation diagram to conduct dose escalation trial.
Subjects will be followed up for 24 weeks after the end of chemotherapy. In this study, the primary efficacy endpoints are maximum tolerated dose (MTD) of cyclophosphamide in combination treatment with bortezomib and fludarabine, complete response rate (CR + CRu), overall response rate (ORR). Main indicators will be evaluated every 2 cycles in the treatment period and every 12 weeks in follow-up period.
Concomitant medications within 2 week before enrollment and during the study process need to be documented. All adverse events will be reported from the time a signed and dated informed consent form is obtained until 30 days following the last dose of study drug.
- Conditions
- Mantle Cell Lymphoma Recurrent
- Being tested
- Combination of Bortezomib, Fludarabine and Cyclophosphamide
- Keywords
- Mantle Cell Lymphoma, Recurrent, Bortezomib, Combination Treatment
- Medical subject headings
- Lymphoma, Mantle-Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of Bortezomib, Fludarabine and CyclophosphamideDrug
bortezomib 1.3mg/m^2 i.v. on days 1, 4, 8 and 11 of each 28-day cycle fludarabine 25mg/m^2 i.v. on days 1~3 of each 28-day cycle cyclophosphamide i.v. on days 1~2 of each 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib,Fludarabine,Cyclophosphamide | Experimental | Not described Receives: Drug: Combination of Bortezomib, Fludarabine and Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical efficacy will be assessed according to the CT scan and bone marrow aspirate and biopsy
The International Working Group (IWG) published the guidelines for response criteria for lymphoma in 1999. These response criteria are based on the reduction in the size of the enlarged lymph node as measured by CT scan and the extent of bone marrow involvement that is determined by bone marrow aspirate and biopsy.
Measured: 2cycle,28-day/cycle
Secondary outcomes (1)
Maximum Tolerated Dose（MTD）of Cyclophosphamide
Maximum tolerated dose (MTD) of cyclophosphamide will be determined in accordance with the standard "3+3" method, testing three dose levels, 150mg/m^2, 200mg/m^2 and 250mg/m^2. Cyclophosphamide dose escalation test will be conducted in the first cycle, with every three patients in a group. Patients' enrollment will be competed among different sites, but futher step should be taken only after the 3 patients in one group complete the first cycle, their efficacy and safety have been completely evaluated, and the notification of going to next step by a CRO company.
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 posted25 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionOct 2013 (estimated)
- Study completionOct 2013 (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 Mantle Cell Lymphoma RecurrentStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Fudan University, First Affiliated Hospital of Zhejiang University, West China Hospital, Ruijin Hospital, Tianjin Medical University Cancer Institute and Hospital, Peking University Cancer Hospital & Institute, Jiangsu Cancer Institute & Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01322776
- Sponsor's protocol ID
- Vel-FC-4003
- Status last verified
- Mar 2011
- First submitted
- 24 Mar 2011
- Last updated
- 25 Mar 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wang XX, Gao Y, Jin J, Cao JN, Feng JF, Wang HQ, Zhang HL, Cai QQ, Li ZM, Jiang WQ, Huang HQ; Lymphoma Committee, Chinese Anti-Cancer Association (CACA). Bortezomib in combination with fludarabine plus cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study. Ann Hematol. 2021 Dec;100(12):2961-2968. doi: 10.1007/s00277-021-04619-4. Epub 2021 Jul 31.
PubMed 34331111
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 and 2 Study of Combination Treatment of Bortezomib, Fludarabine and Cyclophosphamide in Patients With Recurrent Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT01322776
- Acronym / sponsor ID
- Vel-FC-4003
- Conditions
- Mantle Cell Lymphoma Recurrent
- Keywords
- Mantle Cell Lymphoma, Recurrent, Bortezomib, Combination Treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Fudan University, First Affiliated Hospital of Zhejiang University, West China Hospital, Ruijin Hospital, Tianjin Medical University Cancer Institute and Hospital, Peking University Cancer Hospital & Institute, Jiangsu Cancer Institute & Hospital
- Study start
- Mar 2011
- Primary completion
- Oct 2013 (estimated)
- Study completion
- Oct 2013 (estimated)
- First posted
- 25 Mar 2011 (estimated)
- 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 is a multi-center, single arm, open-label, prospective IIS study, which will enroll 40 recurrent MCL patients.The aim is to evaluate the efficacy and safety of bortezomib, fludarabine and cyclophosphamide treatment and also analyze the relationship between NF-kB activity and efficacy of bortezomib treatment and whether NF-kB activity can predict MCL progression.
Detailed description
This is a multi-center, single arm, open-label, prospective IIS study, which will enroll 40 recurrent MCL patients.The aim is to evaluate the efficacy and safety of bortezomib, fludarabine and cyclophosphamide treatment and also analyze the relationship between NF-kB activity and efficacy of bortezomib treatment and whether NF-kB activity can predict MCL progression.
This study consists of three phases: screening/baseline phase, treatment phase and follow-up phase after the end of treatment.
At screening/baseline phase, investigators obtain informed consent form, check the inclusion/exclusion criteria and then collect the following data: demographics, medical history data, vital signs, ECG, MRI/CT/B-ultrasound/X-ray examinations, physical examination, laboratory examinations, pregnancy test (only female) and bone marrow biopsy and aspiration. Pathological diagnosis of mantle cell lymphoma should be established by lymph node biopsy or other tumor histopathological examination and immunophenotyping. At the same time, ECOG-performance status, Fact/GOG-Ntx questionnaire and NF-κB activity will be assessed.
During treatment period, patients will be treated with bortezomib, fludarabine and cyclophosphamide in a 28-day cycle. Patients achieve complete response (CR) or partial response (PR) can receive up to six cycles of VF (C) treatment, while those continue stable disease (SD) will be stopped after 4-cycle treatment and those with progressive disease (PD) will also be stopped after 2-cycle treatment. Due to adverse events, patients may receive reductions or deviate from the intended dose and duration of VF (C) treatment. These adjustments must be in accordance with the regulations in the protocol about the dose and time adjustment.
Maximum tolerated dose (MTD) of cyclophosphamide will be determined in accordance with the standard "3+3" method, testing three dose levels, 150mg/m2, 200mg/m2 and 250mg/m2. Cyclophosphamide dose escalation test will be conducted in the first cycle, with every three patients in a group. Patients' enrollment will be competed among different sites, but further step should be taken only after the 3 patients in one group complete the first cycle, their efficacy and safety have been completely evaluated, and the notification of going to next step by a CRO company. Subjects involved in the cyclophosphamide dose escalation test will continue initial cyclophosphamide dose during the entire study, except for possible dose adjustment determined by investigators due to DLT. After ascertaining MTD, new patients will be administrated with cyclophosphamide at the MTD. According to the dose escalation diagram, up to 18 patients will be involved in dose escalation phase. Subjects who discontinue the treatment due to causes other than DLT in the first cycle should be replaced by new participants to enter dose escalation test. DLT is defined as: a grade 4 neutropenia lasting longer than 7 days, a grade 4 thrombocytopenia, a neutropenic fever, or a grade 3 or above non-hematological toxicity (except for nausea, vomiting and alopecia); a grade 3 or above nausea, vomiting or diarrhea is considered as DLT only if still observed after treatment. Please refer to dose escalation diagram to conduct dose escalation trial.
Subjects will be followed up for 24 weeks after the end of chemotherapy. In this study, the primary efficacy endpoints are maximum tolerated dose (MTD) of cyclophosphamide in combination treatment with bortezomib and fludarabine, complete response rate (CR + CRu), overall response rate (ORR). Main indicators will be evaluated every 2 cycles in the treatment period and every 12 weeks in follow-up period.
Concomitant medications within 2 week before enrollment and during the study process need to be documented. All adverse events will be reported from the time a signed and dated informed consent form is obtained until 30 days following the last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib,Fludarabine,Cyclophosphamide | Experimental | Drug: Combination of Bortezomib, Fludarabine and Cyclophosphamide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female patients 18 years or older;
- Histologically confirmed MCL (Initial diagnosis in hospitals other than sites must be reconfirmed;
- Recurrent patients after first-line or second-line chemotherapy;
- At least including the following characteristic immunophenotype confirmed by immunohistochemistry: CD 20+, CD5+ and cyclin D1+;
- At least 1 measurable site of tumor（long diameter > 2.0 cm by physical examination or > 1.5cm on CT;
Key exclusion criteria (10 listed)
- Peripheral neuropathy or neuropathic pain of grade 2 or worse according to CTC AE 3.0;
- Prior treatment with bortezomib;
- Diagnosed as a malignancy other than MCL（Patients with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded;
- Any experimental or anti-cancer therapy within 4 weeks before the first dose of study drug (including rituximab, alemtuzumab or unconjugated therapeutic antibodies, radiation therapy, etc.);
- Fludarabine resistance or intolerance，exposure to fludarabine within 6 months before screening；History of allergic reaction to compounds containing boron, mannitol, fludarabine or cyclophosphamide;
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 |
|---|---|---|
| Combination of Bortezomib, Fludarabine and Cyclophosphamidebortezomib 1.3mg/m^2 i.v. on days 1, 4, 8 and 11 of each 28-day cycle fludarabine 25mg/m^2 i.v. on days 1~3 of each 28-day cycle cyclophosphamide i.v. on days 1~2 of each 28-day cycle | Drug | Bortezomib,Fludarabine,Cyclophosphamide |
Primary outcome
Clinical efficacy will be assessed according to the CT scan and bone marrow aspirate and biopsy
Time frame: 2cycle,28-day/cycle
The International Working Group (IWG) published the guidelines for response criteria for lymphoma in 1999. These response criteria are based on the reduction in the size of the enlarged lymph node as measured by CT scan and the extent of bone marrow involvement that is determined by bone marrow aspirate and biopsy.
1 secondary outcome
Maximum Tolerated Dose（MTD）of Cyclophosphamide
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 25 Mar 2011.
- Derived from this study: PubMed 34331111Wang XX, Gao Y, Jin J, Cao JN, Feng JF, Wang HQ, Zhang HL, Cai QQ, Li ZM, Jiang WQ, Huang HQ; Lymphoma Committee, Chinese Anti-Cancer Association (CACA). Bortezomib in combination with fludarabine plus cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study. Ann Hematol. 2021 Dec;100(12):2961-2968. doi: 10.1007/s00277-021-04619-4. Epub 2021 Jul 31.
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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.
Huiqiang Huang contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Combination of Bortezomib, Fludarabine and Cyclophosphamide in people with Mantle Cell Lymphoma Recurrent, run by Sun Yat-sen University 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 12 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 25 Mar 2011. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 (huanghq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical efficacy will be assessed according to the CT scan and bone marrow aspirate and biopsy (time frame: 2cycle,28-day/cycle). 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 NCT01322776, 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 25 Mar 2011.