Ignite Creation Date:
2024-05-05 @ 5:30 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00460447
Status:
UNKNOWN
Last Update Posted:
2007-04-16
First Post:
2007-04-12
Brief Title:
Gemtuzumab Ozogamicin Before Allogeneic Stem Cell Transplantation
Sponsor:
University Hospital Carl Gustav Carus
Organization:
University Hospital Carl Gustav Carus
Study Overview
Official Title:
Gentuzumab Ozogamicin Berfore Allogeneic Stem Cell Transplantation in Patients With Relapsed CD33 Acute Myeloid Leukemia
Status:
UNKNOWN
Status Verified Date:
2007-04
Last Known Status:
RECRUITING
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:
Study Design
prospective phase II trial with 30 patients in 1 site
Treatment Scheme
Option 1 Patient 60 years of age with relapse after chemotherapy or 12 months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -6 to -3 TBI 2x2 Gy day -3 to -2 total dose 8 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to day 40 PBSC day 0
Option 2 Patient 60 years of age or younger patients 12 Months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -3 to -1 TBI 1x2 Gy day 0 total dose 2 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to 40 PBSC day 0
prospective phase II trial with 30 patients in 1 site
Treatment Scheme
Option 1 Patient 60 years of age with relapse after chemotherapy or 12 months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -6 to -3 TBI 2x2 Gy day -3 to -2 total dose 8 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to day 40 PBSC day 0
Option 2 Patient 60 years of age or younger patients 12 Months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -3 to -1 TBI 1x2 Gy day 0 total dose 2 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to 40 PBSC day 0
Detailed Description:
ScientificMedical Rationale Objective
Primary
documentation of the extramedullary toxicity of the standard therapy
Secondary
Induction of a persistent remission by the combination of Mylotarg and dose reduced conditioning followed by allogenic hematopoetic stem cell transplantation in patients with relapsed acute myelotic leukemia
Study Design
prospective phase II trial with 30 patients in 1 site
Treatment Scheme
Option 1 Patient 60 years of age with relapse after chemotherapy or 12 months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -6 to -3 TBI 2x2 Gy day -3 to -2 total dose 8 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to day 40 PBSC day 0
Option 2 Patient 60 years of age or younger patients 12 Months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -3 to -1 TBI 1x2 Gy day 0 total dose 2 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to 40 PBSC day 0
Patient Population to be Included
30 patients
Primary and Secondary Efficacy Endpoints
See point ScientificMedical Rationale
Inclusion Criteria Exclusion Criteria
patients with acute myelotic leukemia and expression of CD33 on 5 of blasts in bone marrow
relapse after chemotherapy
relapse after autologous or allogenic hematopoetic stem cell transplantation
pts in 2nd remission after chemotherapy and ineligible for a conventional allogeneic transplantation
age 18-70 years
informed consent of the patient
ASAT ALAT 3fold of upper standard
Bilirubin 2fold of upper standard
ejection fraction 40 in echocardiography
potential donor in accordance with the following priorities
1st HLA-identical related donor HLA A B C and DR
2nd HLA-identical non-related donor with the maximum of 1 allelmismatch DNA typing A B C DRB1 DQB1
Study Procedures
See point Study Design
Safety Endpoints Statistical Considerations
Thirty patients will be treated which will yield a 95 confidence interval for non-relapse mortality with a precision of - 14 Data will be evaluated after groups of 10 and 20 patients If results at those times suggest with greater than 80 confidence that the true rate of day 100 non-relapse mortality exceeds 20 then the trial will be stopped Operationally this will occur if 4 out of 10 or 7 out of 20 patients have non-relapse deaths Should the requisite number of deaths be reached before the 10 or 20 patient benchmarks then the trial will be stopped at that time
A dose reduction of mylotarg from 9 to 6 mgm2 will be performed if the likelihood of grade 4 liver-toxicity as defined by bilirubine AST and symptoms of sinusoidal obstruction syndrome is 20 This will be the case if 4 out of the first ten patients experience grade 4 liver toxicity The second dose of mylotarg will then be omitted in the next ten patients If the rate of liver-toxicity in the next 10 patients remains unchanged the study will be stopped
The stopping rules will be discussed and enforced by the protocol committee and transmitted to each local IRB asap
The following safety endpoints will be documented
1 Incidence of neurological toxicity
2 Incidence of liver toxicity
3 Incidence of acute gastrointestinal toxicity
4 Incidence and severity of mucositis
5 Incidence of pulmonary toxicity
6 Incidence of systemic infections
7 Duration of neutropenia Severe adverse events SAE will have to be reported to the principal investigator within 24 hours after occurrence It will be his responsibility to inform the IRB and the sponsor or the trial if adequate
SAE compromise death before relapse of leukemia illness with life-threatening character severe illness requiring hospitalization illness leading to prolonged disabilities second cancer developing after treatment
SAE will have to be reported on special forms contained in the CRF
Primary
documentation of the extramedullary toxicity of the standard therapy
Secondary
Induction of a persistent remission by the combination of Mylotarg and dose reduced conditioning followed by allogenic hematopoetic stem cell transplantation in patients with relapsed acute myelotic leukemia
Study Design
prospective phase II trial with 30 patients in 1 site
Treatment Scheme
Option 1 Patient 60 years of age with relapse after chemotherapy or 12 months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -6 to -3 TBI 2x2 Gy day -3 to -2 total dose 8 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to day 40 PBSC day 0
Option 2 Patient 60 years of age or younger patients 12 Months after hematopoetic stem cell transplantation Mylotarg 6 mg m² day -21 Mylotarg 3 mg m² day -14 Fludarabin 30 mg m² day -3 to -1 TBI 1x2 Gy day 0 total dose 2 Gy Tacrolimus level adapted from day -3 on Mycophenolat 2 x 1000 mg po from day 0 to 40 PBSC day 0
Patient Population to be Included
30 patients
Primary and Secondary Efficacy Endpoints
See point ScientificMedical Rationale
Inclusion Criteria Exclusion Criteria
patients with acute myelotic leukemia and expression of CD33 on 5 of blasts in bone marrow
relapse after chemotherapy
relapse after autologous or allogenic hematopoetic stem cell transplantation
pts in 2nd remission after chemotherapy and ineligible for a conventional allogeneic transplantation
age 18-70 years
informed consent of the patient
ASAT ALAT 3fold of upper standard
Bilirubin 2fold of upper standard
ejection fraction 40 in echocardiography
potential donor in accordance with the following priorities
1st HLA-identical related donor HLA A B C and DR
2nd HLA-identical non-related donor with the maximum of 1 allelmismatch DNA typing A B C DRB1 DQB1
Study Procedures
See point Study Design
Safety Endpoints Statistical Considerations
Thirty patients will be treated which will yield a 95 confidence interval for non-relapse mortality with a precision of - 14 Data will be evaluated after groups of 10 and 20 patients If results at those times suggest with greater than 80 confidence that the true rate of day 100 non-relapse mortality exceeds 20 then the trial will be stopped Operationally this will occur if 4 out of 10 or 7 out of 20 patients have non-relapse deaths Should the requisite number of deaths be reached before the 10 or 20 patient benchmarks then the trial will be stopped at that time
A dose reduction of mylotarg from 9 to 6 mgm2 will be performed if the likelihood of grade 4 liver-toxicity as defined by bilirubine AST and symptoms of sinusoidal obstruction syndrome is 20 This will be the case if 4 out of the first ten patients experience grade 4 liver toxicity The second dose of mylotarg will then be omitted in the next ten patients If the rate of liver-toxicity in the next 10 patients remains unchanged the study will be stopped
The stopping rules will be discussed and enforced by the protocol committee and transmitted to each local IRB asap
The following safety endpoints will be documented
1 Incidence of neurological toxicity
2 Incidence of liver toxicity
3 Incidence of acute gastrointestinal toxicity
4 Incidence and severity of mucositis
5 Incidence of pulmonary toxicity
6 Incidence of systemic infections
7 Duration of neutropenia Severe adverse events SAE will have to be reported to the principal investigator within 24 hours after occurrence It will be his responsibility to inform the IRB and the sponsor or the trial if adequate
SAE compromise death before relapse of leukemia illness with life-threatening character severe illness requiring hospitalization illness leading to prolonged disabilities second cancer developing after treatment
SAE will have to be reported on special forms contained in the CRF
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