LymphomaPhase 2NCT00765245
Lenalidomide With or Without Rituximab After Standard Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma
A Phase 2 study testing Lenalidomide and Rituximab in people with Lymphoma, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.
Trial summary
RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Lenalidomide and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2008to Nov 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Understand and voluntarily sign an Informed Consent form
- Age > 18 years at time of signing the Informed Consent Form
- Able to adhere to the study visit schedule and other protocol requirements.
- Patients with histological confirmation of diffuse large B cell lymphoma with at least one of the following characteristics:
- High or intermediate IPI score (See Appendix 8.0 for IPI scoring criteria)
- Patients who are still PET scan positive mid therapy with R-CHOP, but, have turned negative after completion of therapy.
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- Low risk International prognostic index ie., an IPI score of <3 if age >60 years or <2 if age is less than or equal to 60 with c-myc positive by Fluorescent In situ Hybridization.
- No other previous lymphoma therapy, hormonal therapy or surgery, except for standard therapy with R-CHOP with or without radiation and with or without prophylactic Methotrexate therapy. Patients must be enrolled within 4-12 weeks of completion of therapy.
- At the time of study entry following standard therapy with R-CHOP±RT, patients should be in complete remission.
- ECOG performance status of ≤ 2 at study entry
- Laboratory test results within these ranges:
- Absolute neutrophil count ≥ 1500/mm³
- Platelet count ≥100K /mm³
- Serum creatinine ≤ 2.0 mg/dL
- Total bilirubin ≤ 1.5 mg/dL
- AST (SGOT) and ALT (SGPT) ≤ 2 x ULN
- Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
- All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the Revlimid REMS® program.
- •Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by the Revlimid REMS® program) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation, if patients are thought to be at an elevated risk of thrombosis.
Who cannot join
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the Informed Consent
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 28 days of baseline.
- Known hypersensitivity to thalidomide.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
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- Any prior use of lenalidomide.
- Concurrent use of other anti-cancer agents or treatments.
- Known positive for HIV or infectious hepatitis, type B or C.
- A diagnosis of deep vein thromboses in the preceding 3 months of study enrollment.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: A Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab as Maintenance Therapy Following Standard Chemotherapy for Patients With High/High-intermediate Risk Diffuse Large B-Cell Lymphoma
RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether lenalidomide is more effective with or without rituximab in treating diffuse large B-cell non-Hodgkin lymphoma.
PURPOSE: This randomized phase II trial is studying lenalidomide to see how well it works when given with or without rituximab after standard chemotherapy in treating patients with diffuse large B-cell non-Hodgkin lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- To assess the 1-year disease-free and relapse-free survival of patients with high- or high/intermediate-risk diffuse large B-cell non-Hodgkin lymphoma treated with maintenance therapy comprising lenalidomide with or without rituximab following standard chemotherapy.
Secondary
- To assess the 2-year disease-free survival of patients treated with these regimens.
- To define the safety and toxicity profile of these regimens.
- To perform antibody-dependent cellular cytotoxicity assays using peripheral blood mononuclear cell samples from these patients.
- To assess the change in the number of natural killer cells by flow cytometric analysis.
- To evaluate cytokines including, but not limited to, sIL-2R, IL-6, IL-15, IL-12, TNF-α, and IFN-γ in these patients.
- To study the KIR genotype receptor and FCγR polymorphisms.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity.
Peripheral blood mononuclear cells are collected periodically for correlative studies. Samples are analyzed for change in the number of natural killer cells by flow cytometry; antibody-dependent cellular cytotoxicity by assay; cytokines; KIR genotype receptor; and FCγR polymorphisms.
After completion of study therapy, patients are followed at 30 days and then every 3 months for 1 year.
- Conditions
- Lymphoma
- Being tested
- Lenalidomide, Rituximab
- Keywords
- stage I adult diffuse large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called Revlimid
Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
LenalidomideDrug
Also called Revlimid
Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles
RituximabDrug
Also called Rituxan
Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
| Study group | Role | What they receive |
|---|---|---|
| Arm I: Lenalidomide | Experimental | Not described Receives: Drug: Lenalidomide |
| Arm II: Lenalidomide and Rituximab IV | Experimental | Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Receives: Drug: Lenalidomide; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free Survival at 1 Year
Disease-free survival is the time from on-treatment to first relapse or death (whichever comes first). Those who are alive and without relapse are censored at the last date known alive.
Measured: From on-treatment date to disease recurrence, up to 1 year
Secondary outcomes (2)
Disease-free Survival at 2 Years
Disease-free survival is the estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method where death is an event, with censoring for non-expired patients at last known date alive.
Measured: From on-treatment date to disease recurrence, up to 2 years
Number of Patients With Each Worst-Grade Toxicity
Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death. Toxicities present at baseline and continuing without change in grade are excluded when considering worst-grade toxicity.
Measured: 30 days after completing treatment, for up to 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Nishitha Reddy, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Nishitha Reddy, MD, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00765245
- Sponsor's protocol ID
- VICC HEM 0835
- Other IDs
- P30CA068485
- Status last verified
- Mar 2016
- First submitted
- 1 Oct 2008
- Last updated
- 11 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Vose JM, Habermann TM, Czuczman MS, Zinzani PL, Reeder CB, Tuscano JM, Lossos IS, Li J, Pietronigro D, Witzig TE. Single-agent lenalidomide is active in patients with relapsed or refractory aggressive non-Hodgkin lymphoma who received prior stem cell transplantation. Br J Haematol. 2013 Sep;162(5):639-47. doi: 10.1111/bjh.12449. Epub 2013 Jul 9.
PubMed 23834234
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab as Maintenance Therapy Following Standard Chemotherapy for Patients With High/High-intermediate Risk Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT00765245
- Acronym / sponsor ID
- VICC HEM 0835
- Conditions
- Lymphoma
- Keywords
- stage I adult diffuse large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2008
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 2 Oct 2008 (estimated)
- Results
- Posted 11 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether lenalidomide is more effective with or without rituximab in treating diffuse large B-cell non-Hodgkin lymphoma.
PURPOSE: This randomized phase II trial is studying lenalidomide to see how well it works when given with or without rituximab after standard chemotherapy in treating patients with diffuse large B-cell non-Hodgkin lymphoma.
Detailed description
OBJECTIVES:
Primary
- To assess the 1-year disease-free and relapse-free survival of patients with high- or high/intermediate-risk diffuse large B-cell non-Hodgkin lymphoma treated with maintenance therapy comprising lenalidomide with or without rituximab following standard chemotherapy.
Secondary
- To assess the 2-year disease-free survival of patients treated with these regimens.
- To define the safety and toxicity profile of these regimens.
- To perform antibody-dependent cellular cytotoxicity assays using peripheral blood mononuclear cell samples from these patients.
- To assess the change in the number of natural killer cells by flow cytometric analysis.
- To evaluate cytokines including, but not limited to, sIL-2R, IL-6, IL-15, IL-12, TNF-α, and IFN-γ in these patients.
- To study the KIR genotype receptor and FCγR polymorphisms.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity.
Peripheral blood mononuclear cells are collected periodically for correlative studies. Samples are analyzed for change in the number of natural killer cells by flow cytometry; antibody-dependent cellular cytotoxicity by assay; cytokines; KIR genotype receptor; and FCγR polymorphisms.
After completion of study therapy, patients are followed at 30 days and then every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I: Lenalidomide | Experimental | Drug: Lenalidomide |
| Arm II: Lenalidomide and Rituximab IV | Experimental | Drug: Lenalidomide, Drug: RituximabPatients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Understand and voluntarily sign an Informed Consent form
- Age > 18 years at time of signing the Informed Consent Form
- Able to adhere to the study visit schedule and other protocol requirements.
- Patients with histological confirmation of diffuse large B cell lymphoma with at least one of the following characteristics:
- No other previous lymphoma therapy, hormonal therapy or surgery, except for standard therapy with R-CHOP with or without radiation and with or without prophylactic Methotrexate therapy. Patients must be enrolled within 4-12 weeks of completion of therapy.
Key exclusion criteria (10 listed)
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the Informed Consent
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 28 days of baseline.
- Known hypersensitivity to thalidomide.
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 |
|---|---|---|
| LenalidomideAlso: RevlimidOrally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. | Drug | Arm I: Lenalidomide |
| LenalidomideAlso: RevlimidLenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles | Drug | Arm II: Lenalidomide and Rituximab IV |
| RituximabAlso: RituxanRituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization. | Drug | Arm II: Lenalidomide and Rituximab IV |
Primary outcome
Disease-free Survival at 1 Year
Time frame: From on-treatment date to disease recurrence, up to 1 year
Disease-free survival is the time from on-treatment to first relapse or death (whichever comes first). Those who are alive and without relapse are censored at the last date known alive.
2 secondary outcomes
Disease-free Survival at 2 Years
Time frame: From on-treatment date to disease recurrence, up to 2 years
Number of Patients With Each Worst-Grade Toxicity
Time frame: 30 days after completing treatment, for up to 13 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23834234Vose JM, Habermann TM, Czuczman MS, Zinzani PL, Reeder CB, Tuscano JM, Lossos IS, Li J, Pietronigro D, Witzig TE. Single-agent lenalidomide is active in patients with relapsed or refractory aggressive non-Hodgkin lymphoma who received prior stem cell transplantation. Br J Haematol. 2013 Sep;162(5):639-47. doi: 10.1111/bjh.12449. Epub 2013 Jul 9.
- Vanderbilt-Ingram Cancer Center, Find a Clinical TrialLink provided by the sponsor.
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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.
Nishitha Reddy, MD principal investigator
Vanderbilt-Ingram Cancer Center
4 sites 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 and Rituximab in people with Lymphoma, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.
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 20 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: finished, as of the sponsor's last update on 11 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 4 sites in United States. 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?
Yes. Results are posted in the registry (first posted 11 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Disease-free Survival at 1 Year (time frame: From on-treatment date to disease recurrence, up to 1 year). 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 NCT00765245, 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 11 Apr 2016.