Ignite Creation Date:
2024-05-05 @ 5:09 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00396968
Status:
WITHDRAWN
Last Update Posted:
2014-02-11
First Post:
2006-11-06
Brief Title:
AMD3100 With Busulfan Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplant for AML and MDS
Sponsor:
Genzyme a Sanofi Company
Organization:
Sanofi
Study Overview
Official Title:
AMD3100 With Busulfan Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes
Status:
WITHDRAWN
Status Verified Date:
2014-02
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:
AMD3100 given in combination with busulfan fludarabine and thymoglobulin ATG for unrelated or HLA nonidentical donors preparative regimen in patients with acute myelogenous leukemia AML myelodysplastic syndromes MDS
This study aims to determine if in AML and MDS patients there is a reduction of malignant cells and enhanced elimination of the leukemia as assessed by progression free survival Secondary goals will be to assess effects on engraftment graft versus host disease GVHD and immune reconstitution
This study aims to determine if in AML and MDS patients there is a reduction of malignant cells and enhanced elimination of the leukemia as assessed by progression free survival Secondary goals will be to assess effects on engraftment graft versus host disease GVHD and immune reconstitution
Detailed Description:
This is a single centre phase III study which will be conducted in two stages The ability of AMD3100 to augment the antileukemic effect of chemotherapy and stem cell transplantation in patients with MDS or with AML in first or subsequent relapse second or greater remission or primary induction failure will be assessed
The primary objective in Stage 1 is to determine an acceptably safe dose utilizing the continual reassessment method CRMThe CRM is a model-based statistical procedure for conducting phase I clinical trials that assigns doses to successive cohorts of patients based on the doses given and outcomes observed toxicity or no toxicity of all previous patients In this sense the method is outcome-adaptive The CRM relies on a simple Bayesian model for the probability of toxicity as a function of dose As the dose-toxicity data in the trial accumulate the Bayesian model learns about the relationship between dose and probability of toxicity Numerous computer simulation studies and the references therein have shown that the CRM has greatly superior properties compared to conventional 33 algorithms This is due to the facts that conventional algorithms are not model-based they only use data from the most recent 6 patients and they tend to stop the trial very early with the consequences that they are very likely to give very unreliable estimates of the toxicity probability at each dose and provide an unreliable recommended maximum tolerated dose MTD
Under the particular version of the CRM being used in this trial following treatment of the first cohort of three patients at the initial dose level 80 µgkg the following decisions are possible
If 0 of the first 3 patients 1 2 and 3 experience toxicity then the method will escalate and the second cohort of patients 4 5 and 6 will be treated at the second dose level 160 µgkg
If either 1 or 2 of the first 3 patients experience toxicity then the method will stay at the starting dose so the second cohort will be treated at the lowest dose level 80 µgkg
If all 3 of the first 3 patients experience toxicity then the posterior probability that the lowest dose is unacceptably toxic will be 0951 and since this exceeds the decision cut-off 090 in the protocol the phase I trial will be terminated with the conclusion that the lowest dose level 80 µgkg is excessively toxic
If the trial continues for all successive cohorts after the first since the decision of which dose to assign utilizes all of the dose-toxicity data from all patients treated previously there are too many possibilities to enumerate For example there are 12 possible outcomes for the second cohort and this number increases exponentially as the trial progresses However at any point in the trial the estimated probability of toxicity at each dose based on the most recent data may easily be estimated and this information made available to the investigators Additional safety provisions are that the middle dose of 160 µgkg may not be skipped when initially escalating from 80 µgkg and the trial will be terminated early with no dose chosen if the lowest dose is excessively toxic
The primary objective in Stage 2 is to determine progression free survival post-allogeneic transplant in terms of time to treatment failure and survival Stage 1 will include both prognostic subgroups CR and not in complete remission NCR In Stage 2 different monitoring rules will be used in CR and NCR subgroups to reflect their very different historical failure rates Additionally all patients treated at the dose selected in Stage 1 will be counted as members of the Stage 2 sample
The primary objective in Stage 1 is to determine an acceptably safe dose utilizing the continual reassessment method CRMThe CRM is a model-based statistical procedure for conducting phase I clinical trials that assigns doses to successive cohorts of patients based on the doses given and outcomes observed toxicity or no toxicity of all previous patients In this sense the method is outcome-adaptive The CRM relies on a simple Bayesian model for the probability of toxicity as a function of dose As the dose-toxicity data in the trial accumulate the Bayesian model learns about the relationship between dose and probability of toxicity Numerous computer simulation studies and the references therein have shown that the CRM has greatly superior properties compared to conventional 33 algorithms This is due to the facts that conventional algorithms are not model-based they only use data from the most recent 6 patients and they tend to stop the trial very early with the consequences that they are very likely to give very unreliable estimates of the toxicity probability at each dose and provide an unreliable recommended maximum tolerated dose MTD
Under the particular version of the CRM being used in this trial following treatment of the first cohort of three patients at the initial dose level 80 µgkg the following decisions are possible
If 0 of the first 3 patients 1 2 and 3 experience toxicity then the method will escalate and the second cohort of patients 4 5 and 6 will be treated at the second dose level 160 µgkg
If either 1 or 2 of the first 3 patients experience toxicity then the method will stay at the starting dose so the second cohort will be treated at the lowest dose level 80 µgkg
If all 3 of the first 3 patients experience toxicity then the posterior probability that the lowest dose is unacceptably toxic will be 0951 and since this exceeds the decision cut-off 090 in the protocol the phase I trial will be terminated with the conclusion that the lowest dose level 80 µgkg is excessively toxic
If the trial continues for all successive cohorts after the first since the decision of which dose to assign utilizes all of the dose-toxicity data from all patients treated previously there are too many possibilities to enumerate For example there are 12 possible outcomes for the second cohort and this number increases exponentially as the trial progresses However at any point in the trial the estimated probability of toxicity at each dose based on the most recent data may easily be estimated and this information made available to the investigators Additional safety provisions are that the middle dose of 160 µgkg may not be skipped when initially escalating from 80 µgkg and the trial will be terminated early with no dose chosen if the lowest dose is excessively toxic
The primary objective in Stage 2 is to determine progression free survival post-allogeneic transplant in terms of time to treatment failure and survival Stage 1 will include both prognostic subgroups CR and not in complete remission NCR In Stage 2 different monitoring rules will be used in CR and NCR subgroups to reflect their very different historical failure rates Additionally all patients treated at the dose selected in Stage 1 will be counted as members of the Stage 2 sample
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