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Trial record 1 of 176 for:    lymphomatoid granulomatosis
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Treatment and Natural History Study of Lymphomatoid Granulomatosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00001379
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : December 14, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date  ICMJE November 3, 1999
First Posted Date  ICMJE November 4, 1999
Last Update Posted Date December 14, 2020
Actual Study Start Date  ICMJE August 7, 1995
Estimated Primary Completion Date February 1, 2030   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
Overall response and long-term efficacy [ Time Frame: After completion of treatment ]
Overall response will be classified as the following: complete remission, partial remission, disease progression or disease stabilization.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
Overall Survival [ Time Frame: Post treatment: every 3 months x 1 year, then every 4 months x 1 year, then every 6 months x 1 year then yearly ]
The response rate will be determined and reported along with a 95% confidence interval.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment and Natural History Study of Lymphomatoid Granulomatosis
Official Title  ICMJE Treatment and Natural History Study of Lymphomatoid Granulomatosis
Brief 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.

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 EPOCH-rituximab (EPOCH-R) chemotherapy (each letter representing a drug). If patients have grade 1 or 2 disease, the 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 (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 patients 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 minimum. 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. 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 EBV related 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)-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 A/B LYG (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, NCI.
  • Patients with any stage of disease will be eligible.
  • Previously untreated and treated patients are eligible.
  • Patients age 12 or older will be eligible.
  • Female patients who are pregnant or lactating are not eligible to receive treatment but can be followed for natural history.

DESIGN:

  • Interferon is used as initial treatment in patients with grades 1 and 2 LYG . Patients will receive interferon for one year past 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphomatoid Granulomatosis
  • Granulomatosis, Lymphomatoid
  • Non-Hodgkins Lymphoma
  • Lymphoproliferative Disorder
Intervention  ICMJE
  • Biological: Interferon
    For LYG Grade 1 and 2: Interferon starting at 7.5 million Units 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 CR.
  • Drug: Rituxan and EPOCH
    For LYG Grade 3: EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituxan) every 3 weeks for 6 cycles.
Study Arms  ICMJE
  • Experimental: 1
    Interferon starting at 7.5 million Units subQ 3 times a week and increasing on the designated schedule,as tolerated. Patients continue taking interferon for 1 year beyond CR. Patients who progress may crossover to receive EPOCH-R.
    Intervention: Biological: Interferon
  • Experimental: 2
    EPOCH-R every 3 weeks for up to 8 cycles, based on response.
    Intervention: Drug: Rituxan and EPOCH
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 17, 2019)
105
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
60
Estimated Study Completion Date  ICMJE February 1, 2034
Estimated Primary Completion Date February 1, 2030   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:

Patients must have a tissue-diagnosis of grade 1, 2 and/or 3 A/B LYG (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, NCI. Final histopathologic classification and pathologic grade will be determined by Stephania Pittaluga, M.D. or her designee.

Patients with any stage of disease will be eligible.

Previously untreated and treated patients are eligible.

Patients age 12 or older will be eligible.

Informed consent must be obtained.

EXCLUSION CRITERIA:

Female patients who are pregnant or lactating are not eligible to receive treatment but can be followed for natural history.

Patients with a history of coronary artery disease with angina pectoris, or a history of congestive heart failure will not be eligible to receive. DA-Epoch-R chemotherapy.

Patients with significant renal (Cr. greater than 1.5 mg/dl or creatinine less than 40 cc/min) or hepatic (bilirubin greater than 2.5 u) dysfunction not due to tumor involvement will not be eligible to receive DA-EPOCH-R chemotherapy.

Patients who in the opinion of the principle investigator are poor psychiatric or medical risk are not eligible.

Patients who received > 450 mg/m2 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: NCI Medical Oncology Referral Office (240) 760-6050 ncimo_referrals@nih.gov
Contact: Mark J Roschewski, M.D. (240) 760-6183 mark.roschewski@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00001379
Other Study ID Numbers  ICMJE 940074
94-C-0074
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark J Roschewski, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date August 10, 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP