Proteasome Inhibition in Acute Promyelocytic Leukemia (PIAPL)
The clinical outcome of relapsed acute promyelocytic leukemia (APL) is poor with current standard of care approaches. Additionally, standard of care warrants an autologous stem cell transplant to be done once molecular remission is achieved. Unfortunately, the majority of our patients cannot afford this procedure. We have previously reported the clinical outcome of relapsed patients who were managed without a stem cell transplants and showed that the event free survival at 5 years is less than 35%. Pre-clinical data reported from our laboratory demonstrates that there is significant synergy between arsenic trioxide (ATO; which is the accepted standard of care agent for relapsed APL) and Bortezomib (a proteasome inhibitor). We have evaluated this combination extensively in-vitro and this data was accepted as an oral presentation at the American Society of Hematology (ASH) meeting in 2011. More recently we have also reported the potential mechanism for this synergy (Poster at ASH 2012). We also have mouse model data which supports these findings. We plan to move this combination of ATO based therapy combined with Bortezomib to a Phase II clinical trial to validate these observations. The anticipated potential is that we will have a combination therapy that is less expensive, cost effective and safe with comparable clinical outcomes to those treated with the more expensive standard of care which includes an autologous stem cell transplant and which the majority of our patients cannot afford.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study to Evaluate the Role of Bortezomib in the Management of Relapsed Acute Promyelocytic Leukemia|
- Safety [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Non hematological toxicity to be monitored
- Efficacy [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Proportion of patients that achieve molecular remission at the end of induction
- Relapse free, event free and overall survival on long term follow up with this protocol.
- Long term toxicity profile of this combination therapy
- Duration of cytopenia with this combination in induction
- Documentation of support care required and total cost of administering this regimen.
- Performance status prior to consolidation therapy, each maintenance course and at the end of the regimen.
- Molecular remission status on follow up for 5 years
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||May 2018|
|Estimated Primary Completion Date:||May 2018 (Final data collection date for primary outcome measure)|
|Experimental: Bortezomib in treatment||
Combination of arsenic trioxide with bortezomib in the treatment of relapsed acute promyelocytic leukemia
Please refer to this study by its ClinicalTrials.gov identifier: NCT01950611
|Contact: Vikram Mathews, MD. DMemail@example.com|
|Department of Haematology, Christian Medical College||Recruiting|
|Vellore, TN, India, 632004|
|Contact: Vikram Mathews 914162282891 firstname.lastname@example.org|
|Sub-Investigator: Biju George, MD. DM|
|Sub-Investigator: Auro Viswabandya, MD. DM|
|Sub-Investigator: Poonkuzhali Balasubramanian, PhD|
|Sub-Investigator: Alok Srivastava, MD|
|Sub-Investigator: Aby Abraham, MD. DM|