Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000989
Status:
COMPLETED
Last Update Posted:
2021-11-04
First Post:
1999-11-02
Brief Title:
The Safety and Effectiveness of Ganciclovir Used Alone or in Combination With Granulocyte-Macrophage Colony Stimulating Factor in the Treatment of Cytomegalovirus CMV of the Eye in Patients With AIDS
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Controlled Randomized Phase II Study of the Safety and Efficacy of Combined Therapy With Ganciclovir and Granulocyte-Macrophage Colony Stimulating Factor Versus Ganciclovir Alone for the Treatment of Sight-Threatening Cytomegalovirus Retinitis in AIDS Patients
Status:
COMPLETED
Status Verified Date:
2021-10
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:
AMENDED To evaluate the effect of sargramostim GM-CSF on modulating the granulocytopenia associated with concomitant DHPG and AZT therapy Phase B in terms of time to development of granulocytopenia as defined by an absolute neutrophil count ANC less than or equal to 750 cellsmm3
Original design To determine if granulocyte-macrophage colony-stimulating factor GM-CSF is helpful in preventing the decreased numbers of white blood cells infection-fighting cells associated with ganciclovir DHPG therapy and to determine if GM-CSF can be safely used in AIDS patients with cytomegalovirus CMV retinitis
AMENDED In ACTG 004 among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy 5 mgkg 5xweek with stable white blood cells WBCabsolute neutrophil counts ANC 7 64 percent required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT 600 mgday was added A mean nadir ANC of 717 cellsml was reached at a mean of 5 weeks of concomitant DHPGAZT therapy in these patients While recovery of depressed ANC occurred following discontinuation of study medications progressive CMV infection most commonly retinitis occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPGAZT Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions The study investigators concluded that the main treatment limiting toxicity of combination DHPGAZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol Original design CMV infection causes inflammation of the retina and can lead to permanent blindness Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease During DHPG treatment however about 30 to 55 percent of patients develop decreased white blood cell counts GM-CSF a naturally occurring human hormone stimulates the bodys bone marrow to produce more white blood cells Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients
Original design To determine if granulocyte-macrophage colony-stimulating factor GM-CSF is helpful in preventing the decreased numbers of white blood cells infection-fighting cells associated with ganciclovir DHPG therapy and to determine if GM-CSF can be safely used in AIDS patients with cytomegalovirus CMV retinitis
AMENDED In ACTG 004 among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy 5 mgkg 5xweek with stable white blood cells WBCabsolute neutrophil counts ANC 7 64 percent required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT 600 mgday was added A mean nadir ANC of 717 cellsml was reached at a mean of 5 weeks of concomitant DHPGAZT therapy in these patients While recovery of depressed ANC occurred following discontinuation of study medications progressive CMV infection most commonly retinitis occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPGAZT Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions The study investigators concluded that the main treatment limiting toxicity of combination DHPGAZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol Original design CMV infection causes inflammation of the retina and can lead to permanent blindness Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease During DHPG treatment however about 30 to 55 percent of patients develop decreased white blood cell counts GM-CSF a naturally occurring human hormone stimulates the bodys bone marrow to produce more white blood cells Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients
Detailed Description:
AMENDED In ACTG 004 among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy 5 mgkg 5xweek with stable white blood cells WBCabsolute neutrophil counts ANC 7 64 percent required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT 600 mgday was added A mean nadir ANC of 717 cellsml was reached at a mean of 5 weeks of concomitant DHPGAZT therapy in these patients While recovery of depressed ANC occurred following discontinuation of study medications progressive CMV infection most commonly retinitis occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPGAZT Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions The study investigators concluded that the main treatment limiting toxicity of combination DHPGAZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol Original design CMV infection causes inflammation of the retina and can lead to permanent blindness Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease During DHPG treatment however about 30 to 55 percent of patients develop decreased white blood cell counts GM-CSF a naturally occurring human hormone stimulates the bodys bone marrow to produce more white blood cells Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients
AMENDED Following completion of Phase A study participants may elect to extend their assigned maintenance therapy DHPG alone or DHPGGM-CSF in combination with AZT therapy Phase B GM-CSF dosing will be titrated as above to maintain a target ANC of 2500-5000 cellsmm3 Those patients receiving DHPGAZT who develop neutropenia ANC less than 750ml on two occasions will begin GM-CSF to maintain a target ANC of 2500-5000 cellsmm3 A similar schedule of clinical ophthalmologic and laboratory evaluations will be followed in order to determine the efficacy and safety of extended maintenance therapy combined with AZT Close monitoring of antiviral CMV HIV and immunomodulatory activity will be assessed This second phase of the study will last for an additional 52 weeks AMENDED Extended to 68 weeks Original design Patients are hospitalized for a minimum of 7 days to begin treatment for CMV retinitis They are randomly assigned to one of two groups to receive DHPG either with or without GM-CSF DHPG is given by intravenous infusion every 12 hours for the first 14 days DHPG maintenance therapy is then given once a day 7 daysweek for the remaining 14 weeks of the study For patients in the DHPG with GM-CSF group the GM-CSF is given by subcutaneous injection for the 16 weeks of the study
AMENDED Following completion of Phase A study participants may elect to extend their assigned maintenance therapy DHPG alone or DHPGGM-CSF in combination with AZT therapy Phase B GM-CSF dosing will be titrated as above to maintain a target ANC of 2500-5000 cellsmm3 Those patients receiving DHPGAZT who develop neutropenia ANC less than 750ml on two occasions will begin GM-CSF to maintain a target ANC of 2500-5000 cellsmm3 A similar schedule of clinical ophthalmologic and laboratory evaluations will be followed in order to determine the efficacy and safety of extended maintenance therapy combined with AZT Close monitoring of antiviral CMV HIV and immunomodulatory activity will be assessed This second phase of the study will last for an additional 52 weeks AMENDED Extended to 68 weeks Original design Patients are hospitalized for a minimum of 7 days to begin treatment for CMV retinitis They are randomly assigned to one of two groups to receive DHPG either with or without GM-CSF DHPG is given by intravenous infusion every 12 hours for the first 14 days DHPG maintenance therapy is then given once a day 7 daysweek for the remaining 14 weeks of the study For patients in the DHPG with GM-CSF group the GM-CSF is given by subcutaneous injection for the 16 weeks of the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| 11047 | REGISTRY | DAIDS ES Registry Number | None |