Mantle Cell LymphomaPhase 2ZOLINZANCT01578343
Vorinostat Plus FND in Relapsed or Refractory Mantle Cell Lymphoma
A Phase 2 study testing Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat in people with Mantle Cell Lymphoma, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
1. Rationale In mantle cell lymphoma, the conventional chemotherapy achieves only temporary responses with a median duration of remissions only from 1 to 2 years. Therefore, mantle cell lymphoma is known as one of the B-cell lymphomas with poor prognosis. Read more about this study
- Who is it for?
- Ages 19 to 75 years
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jun 2012to Feb 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
- Inclusion
- Histologically proven mantle cell lymphoma
- Adequate organ function as defined by the following criteria:
- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ≤2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy
- Total serum bilirubin ≤1.5 x ULN
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100,000/µL
- Hemoglobin ≥9.0 g/dL (may be transfused or erythropoietin treated)
- Serum calcium ≤12.0 mg/dL
- Serum creatinine ≤1.5 x ULN
- Normal potassium and magnesium at baseline
- All patients should be relapsed or refractory patients after previous treatments including chemotherapy .
- At least one measurable lesion (lymph node or tumor mass)
- The size of lesion must be > 1.0cm in the greatest transverse diameter
- ECOG PS 0-2
- Serum HCG test: negative if a patient is female eligible for pregnancy
- Exclusion
- Major surgery or radiation therapy within 4 weeks of starting the study treatment.
- History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease or secondary CNS involvement on CT or MRI scan.
- Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2.
- Pregnancy or breastfeeding.
- Patients with HIV positive
- Patients with HBs antigen positive
- Patients with anti-HCV positive
- History of the use of another HDAC inhibitor: e.g. valproic acid
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Investigation of Vorinostat in Combination With Intravenous Fludarabine, Mitoxantrone, and Dexamethasone in Patients With Relapsed or Refractory Mantle Cell Lymphoma
- Rationale In mantle cell lymphoma, the conventional chemotherapy achieves only temporary responses with a median duration of remissions only from 1 to 2 years. Therefore, mantle cell lymphoma is known as one of the B-cell lymphomas with poor prognosis. Although the treatment outcome of mantle cell lymphoma has been improved since intensive chemotherapy regimens such as HyperCVAD was used, a substantial number of patients are still frequently relapsed after chemotherapy. After relapse, most of them became refractory to various kinds of salvage treatment. That is why the results of most salvage chemotherapy regimens were disappointing. In addition, mantle cell lymphoma generally occurs in elderly people. Thus, intensive salvage chemotherapy may not be feasible for elderly patients. Therefore, an effective, novel combination treatment is urgently needed in relapsed or refractory mantle cell lymphoma patients.
- Hypothesis
- Vorinostat will produce synergism with a combination treatment regimen (Fludarabine, mitoxantrone, dexamethasone, FND) without overlapping toxicity
- Vorinostat maintenance treatment will reduce the relapse rate in patients ineligible for autologous stem cell transplantation.
- Purpose A phase II investigation to determin the effectiveness of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphomain patients with relapsed or refractory mantle cell lymphoma.
Read the detailed description
- Objectives 1.1 Primary objective • To determine the efficacy of vorinostat plus FND as an induction treatment
- Response rate of vorinostat/FND 1.2 Secondary objective
- Survival outcome
- Overall survival and progression-free survival
- To determine the efficacy of vorinostat maintenance treatment
- Relapse rate • Toxicity of vorinostat/FND
- Hematologic and non-hematologic toxicity
- Conditions
- Mantle Cell Lymphoma
- Being tested
- Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat
- Keywords
- fludarabine, mitoxantrone, dexamethasone, relapsed or refractory mantle cell lymphoma, FND regimen, vorinostat, autologous stem cell transplantation
- 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.
Fludarabine, Mitoxantrone, Dexamethasone, VorinostatDrug
Also called 1.Induction treatment (Total 4 cycles) D1-3 Fludarabine D1 Mitoxantrone D1-5 Dexamethasone Vorinostat D1-10 Vorinostat, 2.Consolidation treatment for responders Patients not eligible for transplantation
- Induction treatment (Total 4 cycles) FND D1-3 Fludarabine 25mg/m2 + NS 100mL iv over 30 min D1 Mitoxantrone 10mg/m2 + NS 100mL iv over 30 min D1-5 Dexamethasone 20mg IV or PO every 4 weeks Vorinostat D1-10 Vorinostat 200mg once daily PO (When vorinostat is concurrently administered with FND regimen, vorinostat will be administered 3 hours before chemotherapy)
- Consolidation treatment for responders Patients not eligible for transplantation
- Vorinostat maintenance up to 6 cycles
- 200mg twice daily for 14 consecutive days from D1 - 14 in a 21 day cycle
- Delay of the start of the next cycle by up to 7 days will be acceptable.
- If relapse or progression during maintenance, it will be stopped. Patients eligible for transplantation
- High-dose chemotherapy followed by autologous stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat-FND | Experimental | Vorinostat-fludarabine, mitoxantrone, dexamethasone Induction treatment (Total 4 cycles) FND D1-3 Fludarabine 25mg/m2 + NS 100mL iv over 30 min D1 Mitoxantrone 10mg/m2 + NS 100mL iv over 30 min D1-5 Dexamethasone 20mg IV or PO every 4 weeks Vorinostat D1-10 Vorinostat 200mg once daily PO (When vorinostat is concurrently administered with FND regimen, vorinostat will be administered 3 hours before chemotherapy) Receives: Drug: Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the efficacy of vorinostat plus FND as an induction treatment confirmed by CT or MRI (PET/CT as indicated)
- Response criteria
- Complete response (CR): Disappearance of all detectable clinical and radiographic evidence of disease 2) Partial response (PR): ≥50% decrease in sum of product diameter (SPD) of 6 nodes/nodal masses 3) Stable disease (SD): Disease status is less than PR, but is not PD 4) Progressive disease (PD): Appearance of any new lesions
Measured: A) After 8weeks and 16 weeks of the treatment
Secondary outcomes (1)
To determine the efficacy of vorinostat maintenance treatment, survival outcome and toxicity of vorinostat/FND measured by CT or MRI scan, CTCAE ver 4.0
- Disease status evaluation every 3 months during the 1st two years after enrollment B) Monitoring survival status during the five years after enrollment C) Toxicity evaluation
Measured: every 3 months during the 1st two years after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2012 (estimated)
- Study startJun 2012
- Primary completionSep 2015
- Study completionFeb 2016
Why it stopped: we collected data of a total of 19 patients for an interim analysis. but there are less than 7 responses out of the initial 19 patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Seok Jin Kim
- Responsible party
- Principal investigator, Won Seog Kim, Samsung Medical Center
- Investigators
- Won Seog Kim, MD, PhD, Principal investigator, Samsung Meical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01578343
- Sponsor's protocol ID
- SMC2011-11-102-001
- Acronym
- ZOLINZA
- Status last verified
- Apr 2016
- First submitted
- 30 Mar 2012
- Last updated
- 15 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: we will share collected data with principal investigator in Korea
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Investigation of Vorinostat in Combination With Intravenous Fludarabine, Mitoxantrone, and Dexamethasone in Patients With Relapsed or Refractory Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT01578343
- Acronym / sponsor ID
- ZOLINZA / SMC2011-11-102-001
- Conditions
- Mantle Cell Lymphoma
- Keywords
- fludarabine, mitoxantrone, dexamethasone, relapsed or refractory mantle cell lymphoma, FND regimen, vorinostat, autologous stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: we collected data of a total of 19 patients for an interim analysis. but there are less than 7 responses out of the initial 19 patients.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Collaborators
- Seok Jin Kim
- Study start
- Jun 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 16 Apr 2012 (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.
- Rationale In mantle cell lymphoma, the conventional chemotherapy achieves only temporary responses with a median duration of remissions only from 1 to 2 years. Therefore, mantle cell lymphoma is known as one of the B-cell lymphomas with poor prognosis. Although the treatment outcome of mantle cell lymphoma has been improved since intensive chemotherapy regimens such as HyperCVAD was used, a substantial number of patients are still frequently relapsed after chemotherapy. After relapse, most of them became refractory to various kinds of salvage treatment. That is why the results of most salvage chemotherapy regimens were disappointing. In addition, mantle cell lymphoma generally occurs in elderly people. Thus, intensive salvage chemotherapy may not be feasible for elderly patients. Therefore, an effective, novel combination treatment is urgently needed in relapsed or refractory mantle cell lymphoma patients.
- Hypothesis
- Vorinostat will produce synergism with a combination treatment regimen (Fludarabine, mitoxantrone, dexamethasone, FND) without overlapping toxicity
- Vorinostat maintenance treatment will reduce the relapse rate in patients ineligible for autologous stem cell transplantation.
- Purpose A phase II investigation to determin the effectiveness of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphomain patients with relapsed or refractory mantle cell lymphoma.
Detailed description
- Objectives 1.1 Primary objective • To determine the efficacy of vorinostat plus FND as an induction treatment
- Response rate of vorinostat/FND 1.2 Secondary objective
- Survival outcome
- Overall survival and progression-free survival
- To determine the efficacy of vorinostat maintenance treatment
- Relapse rate • Toxicity of vorinostat/FND
- Hematologic and non-hematologic toxicity
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat-FND | Experimental | Drug: Fludarabine, Mitoxantrone, Dexamethasone, VorinostatVorinostat-fludarabine, mitoxantrone, dexamethasone Induction treatment (Total 4 cycles) FND D1-3 Fludarabine 25mg/m2 + NS 100mL iv over 30 min D1 Mitoxantrone 10mg/m2 + NS 100mL iv over 30 min D1-5 Dexamethasone 20mg IV or PO every 4 weeks Vorinostat D1-10 Vorinostat 200mg once daily PO (When vorinostat is concurrently administered with FND regimen, vorinostat will be administered 3 hours before chemotherapy) |
Who may qualify
- Ages
- 19 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Fludarabine, Mitoxantrone, Dexamethasone, VorinostatAlso: 1.Induction treatment (Total 4 cycles) D1-3 Fludarabine D1 Mitoxantrone D1-5 Dexamethasone Vorinostat D1-10 Vorinostat, 2.Consolidation treatment for responders Patients not eligible for transplantation1. Induction treatment (Total 4 cycles) FND D1-3 Fludarabine 25mg/m2 + NS 100mL iv over 30 min D1 Mitoxantrone 10mg/m2 + NS 100mL iv over 30 min D1-5 Dexamethasone 20mg IV or PO every 4 weeks Vorinostat D1-10 Vorinostat 200mg once daily PO (When vorinostat is concurrently administered with FND regimen, vorinostat will be administered 3 hours before chemotherapy) 2. Consolidation treatment for responders Patients not eligible for transplantation * Vorinostat maintenance up to 6 cycles * 200mg twice daily for 14 consecutive days from D1 - 14 in a 21 day cycle * Delay of the start of the next cycle by up to 7 days will be acceptable. * If relapse or progression during maintenance, it will be stopped. Patients eligible for transplantation * High-dose chemotherapy followed by autologous stem cell transplantation | Drug | Vorinostat-FND |
Primary outcome
To determine the efficacy of vorinostat plus FND as an induction treatment confirmed by CT or MRI (PET/CT as indicated)
Time frame: A) After 8weeks and 16 weeks of the treatment
B) Response criteria 1) Complete response (CR): Disappearance of all detectable clinical and radiographic evidence of disease 2) Partial response (PR): ≥50% decrease in sum of product diameter (SPD) of 6 nodes/nodal masses 3) Stable disease (SD): Disease status is less than PR, but is not PD 4) Progressive disease (PD): Appearance of any new lesions
1 secondary outcome
To determine the efficacy of vorinostat maintenance treatment, survival outcome and toxicity of vorinostat/FND measured by CT or MRI scan, CTCAE ver 4.0
Time frame: every 3 months during the 1st two years after enrollment
Results and safety
The study was stopped early (reason given: we collected data of a total of 19 patients for an interim analysis. but there are less than 7 responses out of the initial 19 patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2016.
- Individual participant dataSharing planned: Yes. we will share collected data with principal investigator in Korea
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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.
Won Seog Kim, MD, PhD principal investigator
Samsung Meical Center
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 Fludarabine, Mitoxantrone, Dexamethasone, Vorinostat in people with Mantle Cell Lymphoma, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: we collected data of a total of 19 patients for an interim analysis. but there are less than 7 responses out of the initial 19 patients.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the efficacy of vorinostat plus FND as an induction treatment confirmed by CT or MRI (PET/CT as indicated) (time frame: A) After 8weeks and 16 weeks of the treatment). 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 15 Apr 2016.