LymphomaPhase 2NCT00983944
Rituximab and Combination Chemotherapy With or Without Bleomycin Sulfate in Treating Patients With Primary Mediastinal Large B-Cell Lymphoma
A Phase 2 study testing bleomycin sulfate, rituximab and EPOCH regimen in people with Lymphoma, run by Ohio State University Comprehensive Cancer Center.
Trial summary
RATIONALE: 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- bleomycin sulfate, rituximab and EPOCH regimen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2009to 25 Apr 2011
- 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed primary mediastinal (thymic) large B-cell lymphoma as defined by WHO classification of lymphoid neoplasms
- Diagnosis must be based on an adequate tissue sample, such as an excisional biopsy or core-needle biopsy
- A paraffin-embedded block of well-fixed lymphoma tissue must be available
- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 10 mm
- No active or untreated CNS lymphoma
- A lumbar puncture is not required in the absence of neurologic symptoms
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1,000/mm^3 (unless related to disease)
- Platelet count ≥ 100,000/mm^3 (unless related to disease)
- Total bilirubin ≤ 2.0 times upper limit of normal (ULN)
- AST and/or ALT ≤ 2.5 times ULN
- Creatinine ≤ 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Ejection fraction ≥ 45% by MUGA or echocardiogram
- Patients with HIV infection are eligible, provided the following criteria are met:
- No evidence of co-infection with hepatitis B or C
- CD4 cell count ≥ 400/mm^3
- No evidence of resistant strains of HIV
- HIV viral load ≤ 10,000 copies HIV RNA/mL (if not on anti-HIV therapy)
- HIV viral load ≤ 50 copies HIV RNA/mL (if on anti-HIV therapy)
- No history of AIDS-defining conditions
- No concurrent uncontrolled illness including, but not limited to, the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situation that would limit compliance with study requirements
- No active secondary malignancy except nonmelanomatous skin cancer
PRIOR CONCURRENT THERAPY:
- No prior cytotoxic chemotherapy or rituximab
- Prior limited course of glucocorticoids allowed
- No other concurrent investigational or commercial anticancer therapies
About this study
Official title: A Randomized Phase II Study of Dose-Adjusted EPOCH-R and R-VACOP-B in Primary Mediastinal (Thymic) Large B-Cell Lymphoma
RATIONALE: 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. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating large B-cell lymphoma.
PURPOSE: This randomized phase II trial is studying how well rituximab and combination chemotherapy work when given with or without bleomycin sulfate in treating patients with primary mediastinal large B-cell lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- To determine the complete response rate based on PET/CT scan criteria in patients with primary mediastinal large B-cell lymphoma (PMLCL) treated with dose-adjusted rituximab, etoposide, doxorubicin hydrochloride, vincristine sulfate, cyclophosphamide, and prednisone with or without bleomycin sulfate.
Secondary
- To characterize the progression-free survival (PFS) of patients treated with these regimens.
- To assess the toxicity profiles associated with these regimens in these patients.
- To determine the prognostic significance of a mid-therapy PET scan and an end-of-therapy PET scan in achieving complete response and in predicting 2-year PFS of patients treated with these regimens.
- To explore the effect of involved-field radiotherapy on 2-year PFS of patients who are PET positive at the end of chemotherapy.
- To explore the efficacy of an end-of-therapy PET/CT scan in predicting which patients can avoid radiotherapy.
- To characterize the overall survival of patients treated with these regimens.
- To prospectively validate a pattern of immunohistochemical staining, including nuclear c-REL, TRAF-1, c-JUN, and Gal1, to accurately distinguish PMLCL from other lymphoid malignancies.
- To determine if levels of soluble CD30 correlate with disease activity in PMLCL.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I (EPOCH-R): Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II (R-VACOP-B): Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10.
In both arms, patients undergo PET/CT scans at baseline, mid-therapy, and after completion of chemotherapy. Patients with stable or progressive disease after completion of chemotherapy are removed from the study. Patients with complete response undergo observation. Patients with partial response undergo involved-field radiotherapy to any area of bulky disease at diagnosis and to any FDG-avid area on PET scan 3-4 weeks after completion of chemotherapy. These patients then undergo additional PET/CT scan at 8-10 weeks after completion of radiotherapy.
Blood samples are collected at baseline, during mid-therapy restaging, and after completion of chemotherapy for analysis of soluble CD30 levels by ELISA. Previously collected tissue samples are obtained for biomarker analysis by IHC.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
- Conditions
- Lymphoma
- Being tested
- bleomycin sulfate, rituximab, EPOCH regimen, cyclophosphamide, doxorubicin hydrochloride
- Keywords
- contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, childhood diffuse large cell lymphoma, stage I childhood large cell lymphoma, stage II childhood large cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood large cell lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Large B-Cell, Diffuse, Dendritic Cell Sarcoma, Interdigitating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bleomycin sulfateBiological
Given IV
rituximabBiological
Given IV
EPOCH regimenDrug
Given IV or orally
cyclophosphamideDrug
Given IV or orally
Given IV or orally
etoposideDrug
Given IV or orally
prednisoneDrug
Given IV or orally
Given IV or orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I (EPOCH-R) | Experimental | Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Drug: EPOCH regimen; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: prednisone; Drug: vincristine sulfate |
| Arm II (R-VACOP-B) | Experimental | Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Receives: Biological: bleomycin sulfate; Biological: rituximab; Drug: EPOCH regimen; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: prednisone; Drug: vincristine sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate
Measured: Up to a year
Secondary outcomes (5)
Two-year progression-free survival
Measured: Up to 2 years
Overall survival
Measured: Up to 3 years
Toxicity as assessed by NCI CTCAE v3.0
Measured: Up to 3 years
Immunohistochemical staining results
Measured: Up to a year
Correlation of soluble CD30 levels with disease activity in PMLCL
Measured: Up to a year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2009 (estimated)
- Study startSep 2009
- Primary completion25 Apr 2011
- Study completion25 Apr 2011
Why it stopped: Inadequate Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive Cancer 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristie A. Blum, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00983944
- Sponsor's protocol ID
- OSU-08178
- Other IDs
- NCI-2011-03123
- Status last verified
- Nov 2017
- First submitted
- 23 Sep 2009
- Last updated
- 30 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Dose-Adjusted EPOCH-R and R-VACOP-B in Primary Mediastinal (Thymic) Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT00983944
- Acronym / sponsor ID
- OSU-08178
- Conditions
- Lymphoma
- Keywords
- contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, childhood diffuse large cell lymphoma, stage I childhood large cell lymphoma, stage II childhood large cell lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Inadequate Accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- Sep 2009 (actual)
- Primary completion
- 25 Apr 2011 (actual)
- Study completion
- 25 Apr 2011 (actual)
- First posted
- 24 Sep 2009 (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: 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. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating large B-cell lymphoma.
PURPOSE: This randomized phase II trial is studying how well rituximab and combination chemotherapy work when given with or without bleomycin sulfate in treating patients with primary mediastinal large B-cell lymphoma.
Detailed description
OBJECTIVES:
Primary
- To determine the complete response rate based on PET/CT scan criteria in patients with primary mediastinal large B-cell lymphoma (PMLCL) treated with dose-adjusted rituximab, etoposide, doxorubicin hydrochloride, vincristine sulfate, cyclophosphamide, and prednisone with or without bleomycin sulfate.
Secondary
- To characterize the progression-free survival (PFS) of patients treated with these regimens.
- To assess the toxicity profiles associated with these regimens in these patients.
- To determine the prognostic significance of a mid-therapy PET scan and an end-of-therapy PET scan in achieving complete response and in predicting 2-year PFS of patients treated with these regimens.
- To explore the effect of involved-field radiotherapy on 2-year PFS of patients who are PET positive at the end of chemotherapy.
- To explore the efficacy of an end-of-therapy PET/CT scan in predicting which patients can avoid radiotherapy.
- To characterize the overall survival of patients treated with these regimens.
- To prospectively validate a pattern of immunohistochemical staining, including nuclear c-REL, TRAF-1, c-JUN, and Gal1, to accurately distinguish PMLCL from other lymphoid malignancies.
- To determine if levels of soluble CD30 correlate with disease activity in PMLCL.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I (EPOCH-R): Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II (R-VACOP-B): Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10.
In both arms, patients undergo PET/CT scans at baseline, mid-therapy, and after completion of chemotherapy. Patients with stable or progressive disease after completion of chemotherapy are removed from the study. Patients with complete response undergo observation. Patients with partial response undergo involved-field radiotherapy to any area of bulky disease at diagnosis and to any FDG-avid area on PET scan 3-4 weeks after completion of chemotherapy. These patients then undergo additional PET/CT scan at 8-10 weeks after completion of radiotherapy.
Blood samples are collected at baseline, during mid-therapy restaging, and after completion of chemotherapy for analysis of soluble CD30 levels by ELISA. Previously collected tissue samples are obtained for biomarker analysis by IHC.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (EPOCH-R) | Experimental | Biological: rituximab, Drug: EPOCH regimen, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: etoposide, Drug: prednisone, Drug: vincristine sulfatePatients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
| Arm II (R-VACOP-B) | Experimental | Biological: bleomycin sulfate, Biological: rituximab, Drug: EPOCH regimen, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: etoposide, Drug: prednisone, Drug: vincristine sulfatePatients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| bleomycin sulfateGiven IV | Biological | Arm II (R-VACOP-B) |
| rituximabGiven IV | Biological | Arm I (EPOCH-R), Arm II (R-VACOP-B) |
| EPOCH regimenGiven IV or orally | Drug | Arm I (EPOCH-R), Arm II (R-VACOP-B) |
| cyclophosphamideGiven IV or orally | Drug | Arm I (EPOCH-R), Arm II (R-VACOP-B) |
| doxorubicin hydrochlorideGiven IV or orally | Drug | Arm I (EPOCH-R), Arm II (R-VACOP-B) |
| etoposideGiven IV or orally | Drug | Arm I (EPOCH-R), Arm II (R-VACOP-B) |
| prednisoneGiven IV or orally | Drug | Arm I (EPOCH-R), Arm II (R-VACOP-B) |
| vincristine sulfateGiven IV or orally | Drug | Arm I (EPOCH-R), Arm II (R-VACOP-B) |
Primary outcome
Complete response rate
Time frame: Up to a year
5 secondary outcomes
Two-year progression-free survival
Time frame: Up to 2 years
Overall survival
Time frame: Up to 3 years
Toxicity as assessed by NCI CTCAE v3.0
Time frame: Up to 3 years
Immunohistochemical staining results
Time frame: Up to a year
Correlation of soluble CD30 levels with disease activity in PMLCL
Time frame: Up to a year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2017.
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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.
Kristie A. Blum, MD principal investigator
Ohio State University Comprehensive Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bleomycin sulfate, rituximab and EPOCH regimen in people with Lymphoma, run by Ohio State University Comprehensive Cancer Center.
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: withdrawn, as of the sponsor's last update on 30 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
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 withdrawn before enrolling participants, so there are no results.
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?
Complete response rate (time frame: Up to a 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 30 Nov 2017.