Lymphomatoid GranulomatosisPhase 2NCT00001379
Treatment and Natural History Study of Lymphomatoid Granulomatosis
A Phase 2 study testing Interferon, Rituxan and EPOCH and Tumor biopsy in people with Lymphomatoid Granulomatosis and Granulomatosis, Lymphomatoid, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will evaluate the response and long-term effects of alpha-interferon in patients with lymphomatoid granulomatosis (LYG). The disease causes proliferation of destructive cells involving the lungs, skin, kidneys, and central nervous system. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Lymphomatoid Granulomatosis, Granulomatosis, Lymphomatoid, Non-Hodgkins Lymphoma
- What is being tested?
- Interferon, Rituxan and EPOCH and Tumor biopsy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 1995to 17 Jan 2025
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a tissue-diagnosis of grade 1, 2 and/or 3 lymphomatoid granulomatosis (LYG) (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI). Final histopathologic classification and pathologic grade will be determined by Stephania Pittaluga, medical doctor (M.D.) or her designee.
- Patients with any stage of disease will be eligible.
- Previously untreated and treated patients are eligible.
- Patients aged 12 or older will be eligible.
Who cannot join
- Patients with a history of coronary artery disease with angina pectoris, or a history of congestive heart failure will not be eligible to receive. etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) chemotherapy.
- Patients with significant renal (serum creatinine (Cr.) greater than 1.5 mg/dl or creatinine clearance less than 40 cc/min) or hepatic (bilirubin greater than 2.5 x upper limit of normal (ULN) dysfunction not due to tumor involvement will not be eligible to receive DA-EPOCH-R chemotherapy.
- Informed consent must be obtained.
- Patients who in the opinion of the principal investigator are poor psychiatric or medical risk are not eligible.
- Patients who received > 450 mg/m^2 doxorubicin and have a cardiac ejection fraction on echocardiogram less than or equal to 40% on protocol entry are not eligible to received DA-EPOCH-R.
- Patients with prior hepatitis B exposure may be included in the study provided that they have hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels below the World Health Organizations cutoff of 100 IU/mL prior to starting therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
This study will evaluate the response and long-term effects of alpha-interferon in patients with lymphomatoid granulomatosis (LYG). The disease causes proliferation of destructive cells involving the lungs, skin, kidneys, and central nervous system.
Patients ages 12 and older who have LYG and who are not pregnant, or breast feeding may be eligible for this study. Alpha interferon or chemotherapy, or both, will be used. Alpha interferon is a protein the body naturally produces. If patients have grade 3 disease, they will usually receive etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)-rituximab (EPOCH-R) chemotherapy (each letter representing a drug). If patients have grade 1 or 2 disease, they will usually receive alpha interferon. If patients have LYG after receiving alpha interferon and/or EPOCH-R, they may receive rituximab alone or with alpha interferon. Rituximab is an antibody, binding to a specific molecule cluster of differentiation 20 (CD20) present on most B-cell lymphomas. Doses of several drugs in EPOCH-R may be increased if patients tolerated them in the previous cycle. If patients respond to EPOCH-R but still have low grade LYG, they may receive alpha interferon. Researchers will also try to obtain a biopsy of patient's lesions, to help in understanding the disease.
Read more
Patients self-administer alpha interferon by injection under the skin three times weekly. They will visit the clinic every 2 to 12 weeks for follow-up. Patients will receive alpha interferon for 1 year after LYG goes away, depending on response. EPOCH-R has these drugs: rituximab by vein on Day 1; prednisone by mouth on Days 1 to 5; etoposide, doxorubicin, and vincristine as a continuous intravenous infusion on Days 1 to 5; and cyclophosphamide by intravenous injection over 1 hour on Day 5. Each cycle lasts 3 weeks: 5 days of chemotherapy and 16 days of no chemotherapy. Etoposide, doxorubicin, and vincristine are infused through a small pump worn by patients. The drugs are given over 5 days through a central intravenous catheter. There are two cycles of EPOCH-R beyond a maximum response, with six cycles maximum. To reduce harm to bone marrow, patients receive granulocyte colony stimulating factor (G-CSF), self-administered by injection under the skin daily for approximately 10 days between chemotherapy cycles. If at the end of therapy, patients have a complete response, treatment will stop. If there is residual low-grade disease, patients may receive alpha interferon. Alpha interferon can have flu-like side effects of headache, fever, chills, and body aches. EPOCH-R drugs can cause gastrointestinal problems, hair loss, and weakness. Granulocyte colony-stimulating factor (G-CSF) can cause bone pain, body aches, and hair thinning. Chemotherapy can cause some patients to develop leukemia.
This study may or may not have a direct benefit for participants. It is not certain whether the new therapy will help decrease tumors. However, knowledge gained may improve the understanding of and treatment for LYG.
...
Read the detailed description
BACKGROUND:
- Lymphomatoid granulomatosis (LYG) is an angiocentric destructive proliferation of lymphoid cells predominantly involving the lungs, skin, kidneys, and central nervous system.
- It is divided into three grades, depending on the degree of necrosis and cellular atypia. The grades of disease are histologically based and do not necessarily correlate with clinical outcome. However, like other Epstein-Barr virus (EBV) related lymphoproliferative disorders (LPD's), LYG can transform into an aggressive large B-cell lymphoma, which would be included within the grade 3 category. It is important to note that not all grade 3 lesions are a large B-cell lymphoma.
- Current evidence shows that LYG is a disease of B cells.
OBJECTIVES:
- To determine the response and long-term efficacy of alpha-Interferon in patients with lymphomatoid granulomatosis (LYG).
- To determine the response and long-term efficacy of dose-adjusted (DA)-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin rituximab (EPOCH-R) chemotherapy in patients with grade 3 LYG or in patients who have failed interferon.
ELIGIBILITY:
- Patients must have a tissue diagnosis of grade 1, 2 and/or 3 LYG (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI).
- Patients with any stage of disease will be eligible.
- Previously untreated and treated patients are eligible.
- Patients aged 12 or older will be eligible.
DESIGN:
- Interferon is used as initial treatment in patients with grades 1 and 2 LYG. Patients will receive interferon for one year past complete remission (CR).
- Patients who progress after or during interferon, and patients with grade 3 LYG will receive aggressive combination chemotherapy with DA-EPOCH-R (rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone).
- Patients who fail one treatment approach may be crossed over to the other.
- A total of 105 patients will be enrolled at this single institution.
- Conditions
- Lymphomatoid Granulomatosis, Granulomatosis, Lymphomatoid, Non-Hodgkins Lymphoma, Lymphoproliferative Disorder
- Being tested
- Interferon, Rituxan and EPOCH, Tumor biopsy, Bone marrow biopsy, Bone marrow aspirate
- Keywords
- Epstein-Barr Virus, Lymphoproliferative Disorder, Viral, Immunosuppression, Lymphoma
- Medical subject headings
- Lymphomatoid Granulomatosis, Lymphoma, Non-Hodgkin, Lymphoproliferative Disorders, Epstein-Barr Virus Infections, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InterferonBiological
Also called IFN
For lymphomatoid granulomatosis (LYG) Grade 1 and 2: Interferon starting at 7.5 million Units subcutaneous (subQ) 3 times a week and increasing on the following schedule: 10 million U; 15 million U; 20 million U; 25 million U; and increased in 5 million U increments, as tolerated. Patients continue taking interferon for 1 year beyond complete remission (CR).
Rituxan and EPOCHDrug
Also called Rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab
For lymphomatoid granulomatosis (LYG) Grade 3: EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) every 3 weeks for 6 cycles.
Tumor biopsyProcedure or surgery
Also called Tumor bx
Baseline (optional).
Bone marrow biopsyProcedure or surgery
Also called BM biopsy
Baseline.
Bone marrow aspirateBiological
Also called BM aspirate
Baseline.
Lumber punctureProcedure or surgery
Also called LP
Baseline.
CTDiagnostic test
Also called Computed tomography
Arm 1: At baseline, then every 4 weeks until on stable dose of interferon or a maximum of 6 monthly scans, then every 3 months while receiving interferon, and following completion of interferon. In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years. Arm 2: At baseline, following cycle 4, and following cycle 6 of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years.
Brain MRIDiagnostic test
Also called Brain magnetic resonance imaging
Arm 1: At baseline, then every 4 weeks until on stable dose of interferon or a maximum of 6 monthly scans, then every 3 months while receiving interferon, and following completion of interferon. In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years (patients with central nervous system (CNS) disease only).
Arm 2: At baseline, following cycle 4, and following cycle 6 of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years (patients with CNS disease only).
EchocardiogramDiagnostic test
Also called Echo
For participants receiving > 450 mg/m^2 doxorubicin.
FDG-PETDiagnostic test
Also called Fluorodeoxyglucose positron emission tomography
Arm 1: Baseline and following completion of interferon. Arm 2: Baseline and following completion of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1-Interferon | Experimental | Interferon starting at 7.5 million Units subcutaneous (subQ) 3 times a week and increasing on the designated schedule, as tolerated. Patients continue taking interferon for 1 year beyond complete remission (CR). Patients who progress may crossover to receive etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R). Receives: Biological: Interferon; Procedure: Tumor biopsy; Procedure: Bone marrow biopsy; Biological: Bone marrow aspirate; Procedure: Lumber puncture; Diagnostic Test: CT; Diagnostic Test: Brain MRI; Diagnostic Test: Echocardiogram; Diagnostic Test: FDG-PET |
| Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) | Experimental | Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) every 3 weeks for up to 6 cycles, based on response. Participants who relapse or progress may crossover to receive interferon. Receives: Drug: Rituxan and EPOCH; Procedure: Tumor biopsy; Procedure: Bone marrow biopsy; Biological: Bone marrow aspirate; Procedure: Lumber puncture; Diagnostic Test: CT; Diagnostic Test: Brain MRI; Diagnostic Test: Echocardiogram; Diagnostic Test: FDG-PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Overall response rate will be classified as the following: complete remission (CR), partial remission (PR), disease progression or disease stabilization measured by the Response Criteria. CR is no evidence of active disease on restaging for at least 2 months duration. All lesions must have decreased by > 75%, be gallium or positron emission tomography (PET) negative (if obtained) and be stable for > 3 months without new lesions appearing. PR is 50% or greater decrease in the sum of the products of the diameters of all measurable lesions for at least one month. Disease progression is 25% or greater progression in the sum of the products of the diameter of any measurable lesion over one month or the appearance or any new lesion consistent with metastatic disease. Disease stabilization is no change in the sum of the products of the diameters of all measurable lesions over two months and no new lesions consistent with disease.
Measured: From study enrollment and throughout treatment, up to a maximum of 40 months for the 2 interferon groups and 8 months for the 2 EPOCH-R groups.
Progression Free Survival (PFS)
PFS is defined as the duration of time from the date of study enrollment until the date of disease relapse, disease progression, death, or last follow-up, whichever occurs first, using the Kaplan-Meier method. Response was assessed by the Lugano Classification Response Criteria for Non-Hodgkin lymphoma (NHL). Disease progression is defined as an increase of ≥ 50% from the product of the perpendicular diameter (PPD) nadir and an increase in longest transverse diameter of a lesion (LDi) or shortest axis perpendicular diameter (SDi) from nadir of >0.5 cm for lesions <2 cm or >1.0 cm for lesions >2 cm.
Measured: Assessed from date of study enrollment until time of disease relapse, disease progression, death, or last follow-up, whichever comes first, up to a maximum of 27 years for the 2 interferon groups and 20 years for the 2 EPOCH-R groups.
Secondary outcomes (1)
Overall Survival (OS)
OS is defined as the time from treatment start date until date of death or date last known alive. The median OS will be determined and reported along with a 95% confidence interval.
Measured: Assessed from date of study enrollment until time of death or last follow-up, whichever comes first, up to a maximum of 27 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start5 May 1995
- Primary completion17 Jan 2025
- Study completion17 Jan 2025
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 Lymphomatoid GranulomatosisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Christopher Melani, MD, National Cancer Institute (NCI)
- Investigators
- Christopher J Melani, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001379
- Sponsor's protocol ID
- 940074
- Other IDs
- 94-C-0074
- Status last verified
- Jun 2025
- First submitted
- 3 Nov 1999
- Last updated
- 19 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Publications
Melani C, Dowdell K, Pittaluga S, Dunleavy K, Roschewski M, Song JY, Calattini S, Kawada JI, Price DA, Chattopadhyay PK, Roederer M, Lucas AN, Steinberg SM, Jaffe ES, Cohen JI, Wilson WH. Interferon alfa-2b in patients with low-grade lymphomatoid granulomatosis and chemotherapy with DA-EPOCH-R in patients with high-grade lymphomatoid granulomatosis: an open-label, single-centre, phase 2 trial. Lancet Haematol. 2023 May;10(5):e346-e358. doi: 10.1016/S2352-3026(23)00029-7. Epub 2023 Mar 31.
PubMed 37011643
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment and Natural History Study of Lymphomatoid Granulomatosis
- ClinicalTrials.gov ID
- NCT00001379
- Acronym / sponsor ID
- 940074
- Conditions
- Lymphomatoid Granulomatosis, Granulomatosis, Lymphomatoid, Non-Hodgkins Lymphoma, Lymphoproliferative Disorder
- Keywords
- Epstein-Barr Virus, Lymphoproliferative Disorder, Viral, Immunosuppression, Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 5 May 1995 (actual)
- Primary completion
- 17 Jan 2025 (actual)
- Study completion
- 17 Jan 2025 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Posted 19 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the response and long-term effects of alpha-interferon in patients with lymphomatoid granulomatosis (LYG). The disease causes proliferation of destructive cells involving the lungs, skin, kidneys, and central nervous system.
Patients ages 12 and older who have LYG and who are not pregnant, or breast feeding may be eligible for this study. Alpha interferon or chemotherapy, or both, will be used. Alpha interferon is a protein the body naturally produces. If patients have grade 3 disease, they will usually receive etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)-rituximab (EPOCH-R) chemotherapy (each letter representing a drug). If patients have grade 1 or 2 disease, they will usually receive alpha interferon. If patients have LYG after receiving alpha interferon and/or EPOCH-R, they may receive rituximab alone or with alpha interferon. Rituximab is an antibody, binding to a specific molecule cluster of differentiation 20 (CD20) present on most B-cell lymphomas. Doses of several drugs in EPOCH-R may be increased if patients tolerated them in the previous cycle. If patients respond to EPOCH-R but still have low grade LYG, they may receive alpha interferon. Researchers will also try to obtain a biopsy of patient's lesions, to help in understanding the disease.
Patients self-administer alpha interferon by injection under the skin three times weekly. They will visit the clinic every 2 to 12 weeks for follow-up. Patients will receive alpha interferon for 1 year after LYG goes away, depending on response. EPOCH-R has these drugs: rituximab by vein on Day 1; prednisone by mouth on Days 1 to 5; etoposide, doxorubicin, and vincristine as a continuous intravenous infusion on Days 1 to 5; and cyclophosphamide by intravenous injection over 1 hour on Day 5. Each cycle lasts 3 weeks: 5 days of chemotherapy and 16 days of no chemotherapy. Etoposide, doxorubicin, and vincristine are infused through a small pump worn by patients. The drugs are given over 5 days through a central intravenous catheter. There are two cycles of EPOCH-R beyond a maximum response, with six cycles maximum. To reduce harm to bone marrow, patients receive granulocyte colony stimulating factor (G-CSF), self-administered by injection under the skin daily for approximately 10 days between chemotherapy cycles. If at the end of therapy, patients have a complete response, treatment will stop. If there is residual low-grade disease, patients may receive alpha interferon. Alpha interferon can have flu-like side effects of headache, fever, chills, and body aches. EPOCH-R drugs can cause gastrointestinal problems, hair loss, and weakness. Granulocyte colony-stimulating factor (G-CSF) can cause bone pain, body aches, and hair thinning. Chemotherapy can cause some patients to develop leukemia.
This study may or may not have a direct benefit for participants. It is not certain whether the new therapy will help decrease tumors. However, knowledge gained may improve the understanding of and treatment for LYG.
...
Detailed description
BACKGROUND:
- Lymphomatoid granulomatosis (LYG) is an angiocentric destructive proliferation of lymphoid cells predominantly involving the lungs, skin, kidneys, and central nervous system.
- It is divided into three grades, depending on the degree of necrosis and cellular atypia. The grades of disease are histologically based and do not necessarily correlate with clinical outcome. However, like other Epstein-Barr virus (EBV) related lymphoproliferative disorders (LPD's), LYG can transform into an aggressive large B-cell lymphoma, which would be included within the grade 3 category. It is important to note that not all grade 3 lesions are a large B-cell lymphoma.
- Current evidence shows that LYG is a disease of B cells.
OBJECTIVES:
- To determine the response and long-term efficacy of alpha-Interferon in patients with lymphomatoid granulomatosis (LYG).
- To determine the response and long-term efficacy of dose-adjusted (DA)-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin rituximab (EPOCH-R) chemotherapy in patients with grade 3 LYG or in patients who have failed interferon.
ELIGIBILITY:
- Patients must have a tissue diagnosis of grade 1, 2 and/or 3 LYG (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI).
- Patients with any stage of disease will be eligible.
- Previously untreated and treated patients are eligible.
- Patients aged 12 or older will be eligible.
DESIGN:
- Interferon is used as initial treatment in patients with grades 1 and 2 LYG. Patients will receive interferon for one year past complete remission (CR).
- Patients who progress after or during interferon, and patients with grade 3 LYG will receive aggressive combination chemotherapy with DA-EPOCH-R (rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone).
- Patients who fail one treatment approach may be crossed over to the other.
- A total of 105 patients will be enrolled at this single institution.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1-Interferon | Experimental | Biological: Interferon, Procedure: Tumor biopsy, Procedure: Bone marrow biopsy, Biological: Bone marrow aspirate, Procedure: Lumber puncture, Diagnostic Test: CT, Diagnostic Test: Brain MRI, Diagnostic Test: Echocardiogram, Diagnostic Test: FDG-PETInterferon starting at 7.5 million Units subcutaneous (subQ) 3 times a week and increasing on the designated schedule, as tolerated. Patients continue taking interferon for 1 year beyond complete remission (CR). Patients who progress may crossover to receive etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R). |
| Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) | Experimental | Drug: Rituxan and EPOCH, Procedure: Tumor biopsy, Procedure: Bone marrow biopsy, Biological: Bone marrow aspirate, Procedure: Lumber puncture, Diagnostic Test: CT, Diagnostic Test: Brain MRI, Diagnostic Test: Echocardiogram, Diagnostic Test: FDG-PETEtoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) every 3 weeks for up to 6 cycles, based on response. Participants who relapse or progress may crossover to receive interferon. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients must have a tissue-diagnosis of grade 1, 2 and/or 3 lymphomatoid granulomatosis (LYG) (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI). Final histopathologic classification and pathologic grade will be determined by Stephania Pittaluga, medical doctor (M.D.) or her designee.
- Patients with any stage of disease will be eligible.
- Previously untreated and treated patients are eligible.
- Patients aged 12 or older will be eligible.
Key exclusion criteria (6 listed)
- Patients with a history of coronary artery disease with angina pectoris, or a history of congestive heart failure will not be eligible to receive. etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) chemotherapy.
- Patients with significant renal (serum creatinine (Cr.) greater than 1.5 mg/dl or creatinine clearance less than 40 cc/min) or hepatic (bilirubin greater than 2.5 x upper limit of normal (ULN) dysfunction not due to tumor involvement will not be eligible to receive DA-EPOCH-R chemotherapy.
- Informed consent must be obtained.
- Patients who in the opinion of the principal investigator are poor psychiatric or medical risk are not eligible.
- Patients who received > 450 mg/m^2 doxorubicin and have a cardiac ejection fraction on echocardiogram less than or equal to 40% on protocol entry are not eligible to received DA-EPOCH-R.
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 |
|---|---|---|
| InterferonAlso: IFNFor lymphomatoid granulomatosis (LYG) Grade 1 and 2: Interferon starting at 7.5 million Units subcutaneous (subQ) 3 times a week and increasing on the following schedule: 10 million U; 15 million U; 20 million U; 25 million U; and increased in 5 million U increments, as tolerated. Patients continue taking interferon for 1 year beyond complete remission (CR). | Biological | Arm 1-Interferon |
| Rituxan and EPOCHAlso: Rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximabFor lymphomatoid granulomatosis (LYG) Grade 3: EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) every 3 weeks for 6 cycles. | Drug | Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| Tumor biopsyAlso: Tumor bxBaseline (optional). | Procedure or surgery | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| Bone marrow biopsyAlso: BM biopsyBaseline. | Procedure or surgery | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| Bone marrow aspirateAlso: BM aspirateBaseline. | Biological | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| Lumber punctureAlso: LPBaseline. | Procedure or surgery | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| CTAlso: Computed tomographyArm 1: At baseline, then every 4 weeks until on stable dose of interferon or a maximum of 6 monthly scans, then every 3 months while receiving interferon, and following completion of interferon. In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years. Arm 2: At baseline, following cycle 4, and following cycle 6 of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years. | Diagnostic test | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| Brain MRIAlso: Brain magnetic resonance imagingArm 1: At baseline, then every 4 weeks until on stable dose of interferon or a maximum of 6 monthly scans, then every 3 months while receiving interferon, and following completion of interferon. In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years (patients with central nervous system (CNS) disease only). Arm 2: At baseline, following cycle 4, and following cycle 6 of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years (patients with CNS disease only). | Diagnostic test | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| EchocardiogramAlso: EchoFor participants receiving > 450 mg/m^2 doxorubicin. | Diagnostic test | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
| FDG-PETAlso: Fluorodeoxyglucose positron emission tomographyArm 1: Baseline and following completion of interferon. Arm 2: Baseline and following completion of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). | Diagnostic test | Arm 1-Interferon, Arm 2-Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin & Rituximab (EPOCH-R) |
Primary outcome
Overall Response Rate (ORR)
Time frame: From study enrollment and throughout treatment, up to a maximum of 40 months for the 2 interferon groups and 8 months for the 2 EPOCH-R groups.
Overall response rate will be classified as the following: complete remission (CR), partial remission (PR), disease progression or disease stabilization measured by the Response Criteria. CR is no evidence of active disease on restaging for at least 2 months duration. All lesions must have decreased by > 75%, be gallium or positron emission tomography (PET) negative (if obtained) and be stable for > 3 months without new lesions appearing. PR is 50% or greater decrease in the sum of the products of the diameters of all measurable lesions for at least one month. Disease progression is 25% or greater progression in the sum of the products of the diameter of any measurable lesion over one month or the appearance or any new lesion consistent with metastatic disease. Disease stabilization is no change in the sum of the products of the diameters of all measurable lesions over two months and no new lesions consistent with disease.
Progression Free Survival (PFS)
Time frame: Assessed from date of study enrollment until time of disease relapse, disease progression, death, or last follow-up, whichever comes first, up to a maximum of 27 years for the 2 interferon groups and 20 years for the 2 EPOCH-R groups.
PFS is defined as the duration of time from the date of study enrollment until the date of disease relapse, disease progression, death, or last follow-up, whichever occurs first, using the Kaplan-Meier method. Response was assessed by the Lugano Classification Response Criteria for Non-Hodgkin lymphoma (NHL). Disease progression is defined as an increase of ≥ 50% from the product of the perpendicular diameter (PPD) nadir and an increase in longest transverse diameter of a lesion (LDi) or shortest axis perpendicular diameter (SDi) from nadir of >0.5 cm for lesions <2 cm or >1.0 cm for lesions >2 cm.
1 secondary outcome
Overall Survival (OS)
Time frame: Assessed from date of study enrollment until time of death or last follow-up, whichever comes first, up to a maximum of 27 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37011643Melani C, Dowdell K, Pittaluga S, Dunleavy K, Roschewski M, Song JY, Calattini S, Kawada JI, Price DA, Chattopadhyay PK, Roederer M, Lucas AN, Steinberg SM, Jaffe ES, Cohen JI, Wilson WH. Interferon alfa-2b in patients with low-grade lymphomatoid granulomatosis and chemotherapy with DA-EPOCH-R in patients with high-grade lymphomatoid granulomatosis: an open-label, single-centre, phase 2 trial. Lancet Haematol. 2023 May;10(5):e346-e358. doi: 10.1016/S2352-3026(23)00029-7. Epub 2023 Mar 31.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
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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.
Christopher J Melani, M.D. principal investigator
National Cancer Institute (NCI)
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 Interferon, Rituxan and EPOCH and Tumor biopsy in people with Lymphomatoid Granulomatosis and Granulomatosis, Lymphomatoid, run by National Cancer Institute (NCI) at 1 site 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 4 inclusion and 6 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 19 Jun 2025. 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 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 19 Jun 2025). 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?
Overall Response Rate (ORR) (time frame: From study enrollment and throughout treatment, up to a maximum of 40 months for the 2 interferon groups and 8 months for the 2 EPOCH-R groups.). 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?
On the ClinicalTrials.gov record for NCT00001379, 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 19 Jun 2025.