Gentuzumab Ozogamicin Berfore Allogeneic Stem Cell Transplantation in Patients With Relapsed CD33+ Acute Myeloid Leukemia
Gentuzumab Ozogamicin Berfore Allogeneic Stem Cell Transplantation in Patients With Relapsed CD33+ Acute Myeloid 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 p.o. 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 p.o. from day 0 to 40 PBSC day 0
Scientific/Medical 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 p.o. 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 p.o. from day 0 to 40 PBSC day 0
Patient Population to be Included:
30 patients
Primary and Secondary Efficacy Endpoints:
See point: Scientific/Medical Rationale
Inclusion Criteria /Exclusion Criteria:
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 mg/m2 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:
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
Inclusion Criteria:
martin.bornhaeuser@uniklinikum-dresden.de+49351458 ext. 4704