National Cancer Institute: Development of Idiotype Tumor Vaccines for Treatment of B-Cell Lymphoma

An Opportunity for a Cooperative Research and Development Agreement (CRADA) is available for collaboration with the NCI Intramural Division of Clinical Sciences for the support of Phase III clinical trials evaluating the efficacy of a protein-based immunoglobulin idiotype vaccine in the treatment of low-grade follicular B-cell lymphoma.

AGENCY:

National Institutes of Health, PHS, DHHS.

ACTION:

Notice of opportunities for Cooperative Research and Development Agreements.

SUMMARY:

Pursuant to the Federal Technology Transfer Act of 1986 (FTTA, 15 U.S.C. § 3710; Executive Order 12591 of April 10, 1987 as amended by the National Technology Transfer and Advancement Act of 1995), the National Cancer Institute (NCI) of the National Institutes of Health (NIH) of the Public Health Service (PHS) of the Department of Health and Human Services (DHHS) seeks a Cooperative Research and Development Agreement (CRADA) with a pharmaceutical or biotechnology company. Any CRADA for development of this technology that includes support for vaccine production, monitoring of Phase III clinical trials and data analysis, or any combination of the above will be considered. The CRADA would have an expected duration of five (5) to seven (7) years. The goals of the CRADA will include the rapid publication of research results and timely commercialization of products, diagnostics and treatments that result from the research. The CRADA Collaborators will have an option to negotiate the terms of an exclusive or nonexclusive commercialization license to subject inventions arising under the CRADA.

ADDRESSES:

Proposals and questions about this CRADA opportunity may be addressed to Dr. Karen Muszynski, Technology Development & Commercialization Branch, National Cancer Institute—Frederick Cancer Research and Development Center, Fairview Center, 1003 West Seventh Street, Room 502, Frederick, MD 20852, Telephone: (301) 846-5222; Facsimile: (301) 846-6820.

EFFECTIVE DATE:

Organizations must submit a proposal summary preferably one page or less, to NCI within 90 days from date of this publication. Guidelines for preparing full CRADA proposals will be communicated shortly thereafter to all respondents with whom initial discussions will have established sufficient mutual interest.

SUPPLEMENTARY INFORMATION:

Technology Available

The National Cancer Institute (NCI) of the National Institutes of Health (NIH) has initiated an FDA-approved, multi-institutional Phase III clinical trial of protein-based immunoglobulin idiotype vaccines for the treatment of low-grade follicular B-cell lymphoma. B-cell tumors are composed of clonally-expanded cells synthesizing a single antibody molecule containing unique variable regions known as idiotypic determinants. The idiotypic determinants of B-cell derived tumors comprise tumor-specific antigens that can serve as a target for immunotherapy. The NCI has previously conducted Phase I and Phase II clinical trials to determine if therapeutically significant immune responses against an autologous, idiotype immunoglobulin protein can be induced in B-cell lymphoma patients (Nature Medicine 5:1171-1177, Oct 1999). Based on results from these studies, the Clinical Research Branch of the NCI has initiated a definitive multi-center Phase III clinical trial of idiotype-specific vaccines for the treatment of low-grade follicular B-cell lymphoma. The NCI, in accordance with the regulations governing the transfer of agents which the Government has taken an active role in developing (37 CFR 404.8), is seeking a pharmaceutical or biotechnology company which can develop these vaccines to a commercially available status to meet the needs of the public and with the best terms for the government.

The NCI specifically seeks a collaborator to support vaccine production and clinical monitoring of the NCI-sponsored Phase III clinical trials in anticipation of the successful commercialization of this technology. Since idiotypic determinants are tumor-specific, the vaccines must be custom-made for each patient. The selected sponsor will collaborate in the development and production of GMP certifiable idiotype vaccines for the treatment of follicular B-cell lymphomas to be used in the Phase III clinical trials leading to a New Drug Application or Biological License Application for a new anti-cancer therapy in anticipation of the successful commercialization of this product. A specific goal of this CRADA will be development of the processes required for large-scale GMP vaccine production and the provision of adequate numbers of GMP produced and formulated idiotype vaccines as needed to complete the clinical development of this agent for the treatment of follicular B-cell lymphoma. The collaborator will be selected based on their ability to provide specific expertise in conversion to GMP vaccine production; experience in preclinical and clinical drug development; experience in the monitoring, evaluation and interpretation of data from investigational agent clinical studies under an IND; and experience in the successful commercialization, marketing and distribution of new cancer therapy products.

The role of the National Cancer Institute in this CRADA may include, but not be limited to:

1. Providing intellectual, scientific, and technical expertise and experience related to the development of idiotype vaccines.

2. Conducting a Phase III clinical trial to evaluate the therapeutic efficacy of idiotype vaccines in association with GM-CSF.

3. Providing scientific and technical expertise in immunological and molecular monitoring of patient responses to the vaccines.

4. Maintenance of an Investigational New Drug Application (IND), including but not limited to submission of Annual Reports, adverse drug experience reports, new protocols, protocol amendments and pharmaceutical data.

5. Publishing research results.

The role of the CRADA Collaborator may include, but not be limited to:

1. Providing significant intellectual, scientific, and technical expertise or experience to the development of processes required for large-scale GMP vaccine production.

2. Provide adequate quantities of GMP certifiable idiotype vaccines for use in the NCI-sponsored Phase III clinical trial, including all necessary pre-clinical safety information and preparation, filing, and submissions to the Drug Master File or IND as required for clinical studies.

3. Providing technical and financial support to facilitate scientific goals, clinical trial monitoring and data analysis.

4. Collaborate in clinical development leading to FDA approval and marketing through participation on a Steering Committee established to guide the commercialization effort.

5. Assume responsibility for the commercialization, marketing and distribution of the vaccine following successful completion of the Phase III trials.

6. Publishing research results.

Selection criteria for choosing the CRADA Collaborator may include, but not be limited to:

1. The ability to collaborate with NCI on the research and development of this technology. The ability to collaborate with NCI can be demonstrated through experience and expertise in this or related areas of technology indicating the ability to contribute intellectually to ongoing research and development.

2. The demonstration of adequate resources to perform the research and development of this technology (e.g. facilities, personnel and expertise) and accomplish objectives according to an appropriate timetable to be outlined in the CRADA Collaborator's proposal.

3. The willingness to commit best effort and demonstrated resources to the research and development of this technology, as outlined in the CRADA Collaborator's proposal.

4. The demonstration of expertise in the commercial development and production of products related to this area of technology.

5. The level of financial support the CRADA Collaborator will provide for CRADA-related Government activities.

6. The willingness to cooperate with the National Cancer Institute in the timely publication of research results.

7. The agreement to be bound by the appropriate DHHS regulations relating to human subjects, and all PHS policies relating to the use and care of laboratory animals.

8. The willingness to accept the legal provisions and language of the CRADA with only minor modification, if any. These provisions govern the distribution of patent rights to CRADA inventions. Generally, the rights of ownership are retained by the organization that is the employer of the inventor, with (1) the grant of a license for research and other Government purposes to the Government when the CRADA Collaborator's employee is the sole inventor, or (2) the grant of an option to elect an exclusive or nonexclusive license to the CRADA Collaborator when the Government employee is the sole inventor.