SOLICITATION NOTICE
A -- SCLERODERMA CYCLOPHOSPHAMIDE OR TRANSPLANTATION STUDY (SCOT)
- Notice Date
- 4/28/2011
- Notice Type
- Presolicitation
- NAICS
- 541712
— Research and Development in the Physical, Engineering, and Life Sciences (except Biotechnology)
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Office of Acquisitions, 6700 B Rockledge Room 3214 MSC7612, Bethesda, Maryland, 20892-7612
- ZIP Code
- 20892-7612
- Solicitation Number
- NIHAI2011125
- Archive Date
- 5/28/2011
- Point of Contact
- George Ralis, Phone: 3014960194, Donald E Collie, Phone: 301-496-0992
- E-Mail Address
-
ralisg@niaid.nih.gov, dcollie@niaid.nih.gov
(ralisg@niaid.nih.gov, dcollie@niaid.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. NIAID's Division of Allergy, Immunology, and Transplantation (DAIT) intends to negotiate on a sole source basis with Duke University (Durham, NC) pursuant to 41 U.S.C.253(c)(1) - which states only one responsible source and no other supplies or services will satisfy agency requirements. The requirement is to complete the clinical trial entitled, Scleroderma Cyclophosphamide or Transplantation (SCOT). This contract would be a follow-on to the existing contract (#N01-AI-05419) in which Duke University is the incumbent contractor. The anticipated period of performance for the new contract is from June 1, 2011 through October 31, 2017. The anticipated contract will consist of a base period of five months and six 12-month option periods. Background A trial entitled "A Randomized, Open-Label, Phase II Multi-Center Study of High Dose Immunosuppressive Therapy Using Total Body Irradiation, Cyclophosphamide, ATGAM, and Autologous Transplantation with Auto-CD34+HPC versus Intravenous Pulse Cyclophosphamide for the Treatment of Severe Systemic Sclerosis" otherwise known as the SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial was developed under the leadership of Dr. Sullivan at Duke University in response to a Broad Agency Announcement (BAA). Prior to the opening of the trial in 2005, a Drug Master File along with Standard Operating Procedures for the production of the cellular product, Auto-CD34+HPC were written and submitted to the FDA. These documents were created in order to ensure consistency in manufacturing across clinical sites. Transplant centers were inspected and qualified for participation in the trial. Version 1.0 of the clinical protocol was submitted to the FDA in August 2004; the first site (Duke) was opened for enrollment in May 2005. Originally 8 transplant centers and 23 rheumatology centers were qualified for participation in the clinical trial although at the current time 8 transplant centers and 11 rheumatology centers remain active. Because of slow enrollment and new data regarding the treatments used in SCOT, the SCOT trial was redesigned in the fall of 2009. Results from recent updates to two previously completed studies were used to estimate the magnitude of the difference of the anticipated differences in survival and event free survival between the two treatment arms of SCOT. This analysis demonstrated that the trial as initially designed was underpowered to detect a difference between the arms at 44 months. The new data revealed that group differences on the order of 20 percentage points could not be anticipated until 54 months following randomization. In order to accommodate both the slow rate of enrollment and the new information on effect size, a hierarchical composite endpoint was developed. The study was amended to include the new endpoint at 54 months with a reduced sample size of 113 subjects. Purpose and Objectives The SCOT trial was originally designed as a phase III trial to determine whether event free survival would be greater in subjects with severe systemic sclerosis receiving high dose immunosuppressive therapy (HDIT) followed by Auto-CD34+HPC transplantation than in subjects who received a 12 month course of pulse intravenous cyclophosphamide at 44 months after randomization. Despite the barriers, the study has randomized 69 subjects to date. The purpose of this contract is to provide funds to complete the clinical study. Enrollment will be closed May 31, 2011. Subject follow up will be completed 54 months following the randomization of the last subject. The last date possible for randomization will be October 1, 2011 A non randomized patient registry has been developed and is currently enrolling subjects. The collection of data from subjects eligible for participation in SCOT but who have declined to do so and are undergoing standard of care, will inform the rheumatology community about the progression of systemic sclerosis (SSc) in the current treatment climate. The registry will help to assess whether the outcomes for subjects enrolled in SCOT differ from those seen in individuals treated in the community. Other tasks to be completed include: flow cytometry studies, high resolution computer assisted tomography studies, and mechanistic studies evaluating the underlying immunologic basis of scleroderma, the effect of treatment on disease status and collection and management of a specimen repository. Project Requirements The consortium of clinical sites developed by the contractor to perform this trial has been maintained and currently consists of 8 transplant centers across the US and Canada. In addition to the transplant centers, 11 rheumatology centers across the US and Canada work to treat and follow subjects from a wider geographic area. Clinical follow up for subjects participating in SCOT needs to be completed. All facets of support for sites will be maintained including support for ongoing IRB approval, protocol development as needed, and maintenance of stem cell lab standards. Follow up will continue for 54 months following the randomization of the last subject. This time period is essential in order to demonstrate efficacy given the sample size and statistical assumptions. Subjects will be seen on the schedule delineated in the clinical protocol. Data will be submitted to the Statistical and Clinical Coordinating Center and publications on the outcome of the trial need to be written. Follow up will be completed for the non-randomized patient registry to inform the rheumatology community about the progression of SSc in the current treatment climate. Long term follow up of mortality and morbidity of subjects originally enrolled in the Scleroderma Lung Study will be obtained in order to understand the long term effectiveness of cyclophosphamide in the treatment of scleroderma lung disease. A repository has been established and is collecting serum, plasma, RNA, DNA and peripheral blood mononuclear cells for future use. The contractor will continue to manage the storage and use of the specimens in the repository. Ongoing mechanistic studies including pharmacokinetics of cyclophosphamide relative to clinical outcome in both arms of SCOT, immunophenotying by flow cytometry, pulmonary response as measured by high resolution compute assisted tomography, molecular analysis of T cell recovery, and the role of endothelial progenitor cells in the pathogenesis of systemic sclerosis will continue. Other Considerations It is critical that the SCOT trial be completed. The subjects have enrolled with the understanding that they will contribute to the medical advances in the field of scleroderma research. To discontinue the trial after enrollment has been closed but before data can be collected to evaluate the primary endpoint is contrary to the basic principles governing clinical research. This cohort of subjects is unique as is the trial design. The samples collected during the trial are also a unique resource. Studying the specimens in concert with complete clinical data may permit further understanding of the immunologic defect in scleroderma. • The contractor has assembled a unique consortium of sites and investigators to perform the trial. The cooperative clinical structure involving the rheumatology centers and transplant centers was created by Duke to ease the travel burden and provide optimal care for subjects during the period covered by the trial. • Complex contracts based on per patient milestones were developed and implemented by Duke to each of the sites participating in the SCOT trial. Staff is currently employed at Duke to work exclusively on these contracting processes. • Duke has developed a website, advertising, and educational materials to aid in the conduct of the trial. All of these materials require IRB review before they can be made public. Duke's IRB has performed this service. These materials would need to be re-reviewed by another institution's IRB potentially causing delays. • It is ethically imperative that the work of caring for subjects enrolled in a clinical trial not be interrupted. • It is not in the government's interest to transfer the infrastructure Duke has developed to another institution. Operationally, the most efficient course is for Duke to continue to hold the prime contract and manage the structure they have created to complete the SCOT trial. To transfer the administrative responsibilities and all of the contracts would run the risk of an interruption to clinical care and data collection and of compromise to the integrity of the project.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NIAID/NIHAI2011125/listing.html)
- Record
- SN02435563-W 20110430/110428234512-e3a055606954c423b4a4606326f96081 (fbodaily.com)
- Source
-
FedBizOpps Link to This Notice
(may not be valid after Archive Date)
| FSG Index | This Issue's Index | Today's FBO Daily Index Page |