Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00033956
Status:
SUSPENDED
Last Update Posted:
2005-06-24
First Post:
2002-04-17
Brief Title:
Evaluation of M40403 for the Prevention of Dose Limiting Toxicities of High Dose IL-2
Sponsor:
MetaPhore Pharmaceuticals
Organization:
MetaPhore Pharmaceuticals
Study Overview
Official Title:
Phase III Open Label Dose Escalation and Double-Blind Placebo-Controlled Evaluation of M40403 for the Prevention of the Dose Limiting Toxicities of High Dose IV Bolus IL-2 Treatment of Metastatic Melanoma or Renal Cell Carcinoma
Status:
SUSPENDED
Status Verified Date:
2002-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The clinical use of IL-2 is currently limited by development of dose-dependent hypotension systolic blood pressure SBP 90 mm Hg The overall outcome is constant across sites with 20-50 of the patients requiring ICU management because of unresponsive hypotension and hyporeactivity loss of response to vasoconstrictors Because of the dose-limiting side effects the duration of IL-2 dosing is frequently curtailed Thus hemodynamic toxicities have limited the usefulness of IL-2 therapy M40403 has prevented both the hypotension and hyporeactivity associated with IL-2 treatment in preclinical studies This trial will study the safety and efficacy of M40403 in the prevention or reduction of hypotension in patients receiving IL-2 therapy
Detailed Description:
High-dose interleukin-2 IL-2 therapy is currently indicated for treatment of metastatic renal cell carcinoma and metastatic malignant melanoma and has been associated with a 5-15 long-term clinical response In addition IL-2 therapy is showing promise in treatment of acute myelogenous leukemia non-Hodgkins lymphoma and breast cancer and in improving immunologic function in patients with AIDS However the major dose-limiting toxicity of IL-2 hypotension severely limits the usefulness of IL-2 therapy
Because of the unresponsive hypotension and loss of response to exogenously administered vasopressors 20-50 of the patients receiving high dose IL-2 therapy require ICU management These dose-limiting side effects frequently necessitate curtailing the full period of IL-2 dosing in order to reverse the hypotension and prevent subsequent renal dysfunction Thus hemodynamic toxicities have limited the usefulness of IL-2 therapy A course of IL-2 therapy requires long hospitalization and intense patient monitoring during administration As a consequence despite favorable long-term response few sites offer this treatment
The availability of an agent that prevents IL-2-induced hypotension without adversely affecting the therapeutic mechanism of IL-2 would markedly facilitate IL-2 administration and at a minimum would maximize the number of patients who could receive the full regimen of IL-2 The reduction in IL-2 toxicity may also enable higher doses andor more frequent dosing of IL-2 to be used with the potential of higher success of tumor response Because M40403 may decrease the toxicity of IL-2 co-administration of M40403 may make it possible to broaden the clinical use of IL-2 to conditions where it is not currently indicated
The indication to be studied is for use in the prevention or reduction of hypotension associated with interleukin-2 IL-2 therapy in patients with metastatic melanoma and renal cell carcinoma
The study is divided into a sequential dose escalation phase followed by the expansion of the selected dose in a double-blind placebo-controlled evaluation phase Patients with metastatic or inoperable melanoma and renal cell carcinoma will be receiving high dose IL-2 per approved labeling as two 5-day sequences M40403 will be administered by intravenous infusion over 30 minutes prior to each intravenous administration of high dose IL-2 Sequential panels of patients will receive increasing doses of M40403 along with IL-2 until an active dose is determined and an MTD is reached Patients will be followed to determine the effects of M40403 on development of markers of IL-2 dose-limiting toxicity including hypotension tachycardia index of renal perfusion cumulative dose of pressor required and cumulative dose of IL-2 administered Approximately 48 patients will be studied
Because of the unresponsive hypotension and loss of response to exogenously administered vasopressors 20-50 of the patients receiving high dose IL-2 therapy require ICU management These dose-limiting side effects frequently necessitate curtailing the full period of IL-2 dosing in order to reverse the hypotension and prevent subsequent renal dysfunction Thus hemodynamic toxicities have limited the usefulness of IL-2 therapy A course of IL-2 therapy requires long hospitalization and intense patient monitoring during administration As a consequence despite favorable long-term response few sites offer this treatment
The availability of an agent that prevents IL-2-induced hypotension without adversely affecting the therapeutic mechanism of IL-2 would markedly facilitate IL-2 administration and at a minimum would maximize the number of patients who could receive the full regimen of IL-2 The reduction in IL-2 toxicity may also enable higher doses andor more frequent dosing of IL-2 to be used with the potential of higher success of tumor response Because M40403 may decrease the toxicity of IL-2 co-administration of M40403 may make it possible to broaden the clinical use of IL-2 to conditions where it is not currently indicated
The indication to be studied is for use in the prevention or reduction of hypotension associated with interleukin-2 IL-2 therapy in patients with metastatic melanoma and renal cell carcinoma
The study is divided into a sequential dose escalation phase followed by the expansion of the selected dose in a double-blind placebo-controlled evaluation phase Patients with metastatic or inoperable melanoma and renal cell carcinoma will be receiving high dose IL-2 per approved labeling as two 5-day sequences M40403 will be administered by intravenous infusion over 30 minutes prior to each intravenous administration of high dose IL-2 Sequential panels of patients will receive increasing doses of M40403 along with IL-2 until an active dose is determined and an MTD is reached Patients will be followed to determine the effects of M40403 on development of markers of IL-2 dose-limiting toxicity including hypotension tachycardia index of renal perfusion cumulative dose of pressor required and cumulative dose of IL-2 administered Approximately 48 patients will be studied
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