Ignite Creation Date:
2024-05-05 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00143975
Status:
COMPLETED
Last Update Posted:
2010-08-12
First Post:
2005-08-31
Brief Title:
Gemtuzumab Ozogamicin in Combination With A-HAM in Refractory AML GO-A-HAM
Sponsor:
University of Ulm
Organization:
University of Ulm
Study Overview
Official Title:
Phase II Study on Gemtuzumab Ozogamicin in Combination With All-trans-Retinoic Acid High-dose Cytarabine and Mitoxantrone in Patients With Primary Refractory Acute Myeloid Leukemia
Status:
COMPLETED
Status Verified Date:
2010-08
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:
GO-A-HAM
Gemtuzumab Ozogamicin 3gm² day 1 Cytarabine 3gm² bid days 1-3 Mitoxantrone 12mgm² days 23 All-trans Retinoic acid 45mgm² days 4-6 and 15 mgm² days 7-28
Gemtuzumab Ozogamicin 3gm² day 1 Cytarabine 3gm² bid days 1-3 Mitoxantrone 12mgm² days 23 All-trans Retinoic acid 45mgm² days 4-6 and 15 mgm² days 7-28
Detailed Description:
Primary refractory AML is associated with an extremely poor prognosis 12 In the AMLHD93 trial conducted by the AMLSG ULM patients refractory to the first induction therapy with ICE idarubicin cytarabine etoposide had an overall survival of 12 after 5 years 1 All patients alive in this cohort had received allogeneic transplantation Therefore we assigned allogeneic transplantation in our consecutive trial AMLHD98A to all primary refractory patients 3 However the main problem in this patient group remains achieving a partial PR or complete CR remission to a salvage therapy Additionally the pre-transplant disease status is an important prognostic factor in most studies of allogeneic transplantation regardless dose intensified or dose reduced conditioning regimens are used 456 Since 1993 in all studies of the German-Austrian-AMLSG response-adapted treatment strategies had been used Within the AMLHD93 trial refractory patients were assigned to an intensified second induction regimen with S-HAM age55 years 7 or HAM age 55 to 60 years 1 and in the AMLHD98A trial with A-HAM 3 The incorporation of all-trans-retinoic acid was based on in vitro data 8-13 and by our randomised AMLHD98B study for elderly AML-patients showing a benefit in primary response and survival for patients assigned to standard induction therapy in combination with ATRA 14
To compare the different salvage therapy strategies we performed an as-treated analysis in primary refractory patients of the different cohorts Although refractory to the first induction therapy with ICE nine patients received a second cycle ICE The results summarized in table 1 showed an improved response rate CR and PR for patients treated with the A-HAM protocol and thus leading to a higher proportion of patients receiving an allogeneic transplantation Survival analysis showed so far no difference between the 4 different groups Gemtuzumab ozogamicin GO is a humanized anti-CD33 conjugated to Calicheamicin The efficacy and the toxicity profile has been evaluated in several studies so far the substance is approved for the monotherapy in relapsed AML-patients in a dose of 9mgm² q 14d 15 However used as a single agent the efficacy is limited and not durable Therefore several trials have evaluated GO in combination with conventional chemotherapy 1617 In the MRC study a dose of 6 mgm² given once at day 1 was associated with an increased liver toxicity and therefore the study continues with a dose of 3 mgm² once at day 1 of induction therapy 17 In summary the available data for combination therapy showed efficacy of GO in phase II trials The dose limiting toxicity was defined in the MRC trial at 6 mgm² Therefore we consider GO in combination with A-HAM for primary refractory adult AML patients Because all primary refractory patients are candidates for an allogeneic transplantation special considerations have to be taken with respect to the development of VOD after allogeneic transplantation One recent report suggests a substantial risk for VOD for patients receiving an allogeneic transplantation after a therapy with GO 18 In this report the odds ratio for VOD after a therapy with GO within 35 months before allogeneic transplantation was 216 95-confidence interval 42-1122 However this report is based on 62 patients and the dosage of GO used was 6mgm² and 9mgm² Therefore holding in mind the risk of VOD after GO exposure and the extremely poor prognosis of primary refractory patients the treatment approach combining A-HAM with GO with a dose of 3mgm² is justified
To compare the different salvage therapy strategies we performed an as-treated analysis in primary refractory patients of the different cohorts Although refractory to the first induction therapy with ICE nine patients received a second cycle ICE The results summarized in table 1 showed an improved response rate CR and PR for patients treated with the A-HAM protocol and thus leading to a higher proportion of patients receiving an allogeneic transplantation Survival analysis showed so far no difference between the 4 different groups Gemtuzumab ozogamicin GO is a humanized anti-CD33 conjugated to Calicheamicin The efficacy and the toxicity profile has been evaluated in several studies so far the substance is approved for the monotherapy in relapsed AML-patients in a dose of 9mgm² q 14d 15 However used as a single agent the efficacy is limited and not durable Therefore several trials have evaluated GO in combination with conventional chemotherapy 1617 In the MRC study a dose of 6 mgm² given once at day 1 was associated with an increased liver toxicity and therefore the study continues with a dose of 3 mgm² once at day 1 of induction therapy 17 In summary the available data for combination therapy showed efficacy of GO in phase II trials The dose limiting toxicity was defined in the MRC trial at 6 mgm² Therefore we consider GO in combination with A-HAM for primary refractory adult AML patients Because all primary refractory patients are candidates for an allogeneic transplantation special considerations have to be taken with respect to the development of VOD after allogeneic transplantation One recent report suggests a substantial risk for VOD for patients receiving an allogeneic transplantation after a therapy with GO 18 In this report the odds ratio for VOD after a therapy with GO within 35 months before allogeneic transplantation was 216 95-confidence interval 42-1122 However this report is based on 62 patients and the dosage of GO used was 6mgm² and 9mgm² Therefore holding in mind the risk of VOD after GO exposure and the extremely poor prognosis of primary refractory patients the treatment approach combining A-HAM with GO with a dose of 3mgm² is justified
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