Ignite Creation Date:
2024-05-05 @ 11:36 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00092222
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2004-09-21
Brief Title:
Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castlemans Disease With Laboratory and Clinical Correlates of Disease Activity
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will gain information about a rare disorder called KSHV-associated multicentric Castleman s disease MCD KSHV a virus causes several kinds of cancer including some forms of MCD KSHV stands for the Kaposi s sarcoma herpes virus also called human herpes virus-8 or HHV-8 Researchers want to understand the biology of KSHV-MCD to identify how this disease causes illness and to find ways to treat it There is no standard therapy effective for all cases of KSHV-MCD The disease is often fatal and about half the people who have it die within 2 years of diagnosis
Participants ages 18 and older may be eligible for this study Participation entails more drawing of blood and having repeated tumor biopsies than if patients received treatment in a non-research setting Researchers would like to learn more about the relationship of KSHV and Castleman s disease symptoms and they want to obtain at least three biopsies in this study
There are some side effects of experimental therapy that participants may take for KSHV-MCD Zidovudine or Retrovir is used at a high dose It is given orally or through a vein four times daily for 7 days or longer Zidovudine can cause nausea vomiting decreased bone marrow function and decreased blood counts Combined with valganciclovir or Valcyte it is likely to be more toxic to bone marrow Valganciclovir can cause problems with bone marrow function leading to low blood counts sterility and defects in a fetus Combined with zidovudine valganciclovir may cause more toxicity to the bone marrow It is given twice daily for 7 days or longer Bortezomib or Velcade is given for a few seconds by a rapid push through a needle into the vein It is given twice weekly for four doses and then stopped for 1 week Bortezomib can sometimes cause low blood pressure it also can cause gastrointestinal problems and a low blood platelet count Rituximab and liposomal doxorubicin are drugs given by a catheter into a vein Interferon-alpha is given by injection into the skin Those drugs are not experimental but their use in Castleman s disease is experimental
Some participants may be treated with a combination of chemotherapy followed by interferon-alpha Interferon-alpha is infected into the skin by a needle The natural form of interferon is produced by the body and helps to control viral infections KSHV decreases the effect of the body s interferon and the researchers want to see if giving higher doses of interferon will help to control KSHV infection
A positron emission tomography PET scan for research purposes only may be done up to three times a year A radioactive sugar molecule called fluorodeoxyglucose or FDG is used It is believed that activated lymphocytes that may be found in participants disease might use more FDG because these cells burn more glucose fuel
This study may or may not have a direct benefit for participants However detailed assessments made throughout the study may provide information to help the doctors treat KSHV-MCD better
Participants ages 18 and older may be eligible for this study Participation entails more drawing of blood and having repeated tumor biopsies than if patients received treatment in a non-research setting Researchers would like to learn more about the relationship of KSHV and Castleman s disease symptoms and they want to obtain at least three biopsies in this study
There are some side effects of experimental therapy that participants may take for KSHV-MCD Zidovudine or Retrovir is used at a high dose It is given orally or through a vein four times daily for 7 days or longer Zidovudine can cause nausea vomiting decreased bone marrow function and decreased blood counts Combined with valganciclovir or Valcyte it is likely to be more toxic to bone marrow Valganciclovir can cause problems with bone marrow function leading to low blood counts sterility and defects in a fetus Combined with zidovudine valganciclovir may cause more toxicity to the bone marrow It is given twice daily for 7 days or longer Bortezomib or Velcade is given for a few seconds by a rapid push through a needle into the vein It is given twice weekly for four doses and then stopped for 1 week Bortezomib can sometimes cause low blood pressure it also can cause gastrointestinal problems and a low blood platelet count Rituximab and liposomal doxorubicin are drugs given by a catheter into a vein Interferon-alpha is given by injection into the skin Those drugs are not experimental but their use in Castleman s disease is experimental
Some participants may be treated with a combination of chemotherapy followed by interferon-alpha Interferon-alpha is infected into the skin by a needle The natural form of interferon is produced by the body and helps to control viral infections KSHV decreases the effect of the body s interferon and the researchers want to see if giving higher doses of interferon will help to control KSHV infection
A positron emission tomography PET scan for research purposes only may be done up to three times a year A radioactive sugar molecule called fluorodeoxyglucose or FDG is used It is believed that activated lymphocytes that may be found in participants disease might use more FDG because these cells burn more glucose fuel
This study may or may not have a direct benefit for participants However detailed assessments made throughout the study may provide information to help the doctors treat KSHV-MCD better
Detailed Description:
Background
Multicentric Castlemans disease MCD is a rare but lethal Kaposis sarcoma-associated herpesvirus KSHV associated lymphoproliferative disorder with a median survival of 2 years It occurs more often in HIV-infected individuals than those without HIV infection The poor prognosis is not fully explained by the underlying HIV as the HIV-negative cases appear to have no survival advantage over the HIV-positive cohort The disease has no defined standard treatment and has not been prospectively studied in a comprehensive manner
KSHV-MCD may provide a model for the development of targeted oncolytic virotherapy or other pathogenesis-based approaches to viral-associated malignancies In KSHV-MCD viral encoded tyrosine kinase genes appear to be possible targets to exploit in a virotherapy approach Specific viral encoded genes appear to convert zidovudine and ganciclovir or valganciclovir into toxic phosphorylated moieties within the KSHV-infected tumor cells to specifically target the KSHV-infected cells thus leading to specific cell death If successful this could have direct therapeutic benefit to participants and also provide a model for further development of this approach in other tumors
Objectives
-To study and describe the natural history of KSHV-MCD
Eligibility
Age greater than or equal to 18 years
Biopsy proven KSHV-associated MCD
Design
Natural History study
Inclusion of treatment as needed with guidelines for preliminary investigation of a variety of specific treatments of interest
High-dose zidovudine and ganciclovir
High-dose zidovudine and ganciclovir and bortezomib
Sirolimus
Rituximab with liposomal doxorubicin followed by interferon-alpha
Rituximab with EPOCH chemotherapy
Multicentric Castlemans disease MCD is a rare but lethal Kaposis sarcoma-associated herpesvirus KSHV associated lymphoproliferative disorder with a median survival of 2 years It occurs more often in HIV-infected individuals than those without HIV infection The poor prognosis is not fully explained by the underlying HIV as the HIV-negative cases appear to have no survival advantage over the HIV-positive cohort The disease has no defined standard treatment and has not been prospectively studied in a comprehensive manner
KSHV-MCD may provide a model for the development of targeted oncolytic virotherapy or other pathogenesis-based approaches to viral-associated malignancies In KSHV-MCD viral encoded tyrosine kinase genes appear to be possible targets to exploit in a virotherapy approach Specific viral encoded genes appear to convert zidovudine and ganciclovir or valganciclovir into toxic phosphorylated moieties within the KSHV-infected tumor cells to specifically target the KSHV-infected cells thus leading to specific cell death If successful this could have direct therapeutic benefit to participants and also provide a model for further development of this approach in other tumors
Objectives
-To study and describe the natural history of KSHV-MCD
Eligibility
Age greater than or equal to 18 years
Biopsy proven KSHV-associated MCD
Design
Natural History study
Inclusion of treatment as needed with guidelines for preliminary investigation of a variety of specific treatments of interest
High-dose zidovudine and ganciclovir
High-dose zidovudine and ganciclovir and bortezomib
Sirolimus
Rituximab with liposomal doxorubicin followed by interferon-alpha
Rituximab with EPOCH chemotherapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-0275 | None | None | None |