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Cell Therapy for Pediatric Diseases: A Growing Frontier Production Assistance for Cellular Therapies (PACT) Workshop

Executive Summary

On September 14-15, 2011, the NHLBI sponsored a workshop through the Production Assistance for Cellular Therapies (PACT) program. The goal of this workshop was to identify the unique opportunities and challenges of developing cellular therapies in the pediatric population and to identify potential strategies to facilitate the development of new, effective cellular therapies in diseases primarily affecting children. The diseases and conditions affecting pediatric patients for which cellular therapeutics may offer the only potential curative treatment at this time are almost exclusively rare diseases. The ethical considerations of conducting clinical trials in pediatric patients combined with challenges of conducting trials involving cellular therapy for rare disorders were considered in the workshop. The speakers, panelists and participants identified the unmet needs delaying the advancement of clinical research for these childhood conditions and proposed strategies to ameliorate the obstacles hindering the development of novel therapeutics.

Presentations and Discussions

The workshop consisted of three scientific sessions. Each session focused on a defined group of diseases and disorders affecting the pediatric population. Multiple therapeutic approaches were compared and contrasted for those disorders and diseases where there are completed, ongoing or planned trials. The presentations identified key obstacles that the investigators encountered in the development and/or implementation of their clinical trials and the solutions they employed to address these challenges. In addition to the speakers, a panel composed of ethicists, statisticians, regulatory experts, and parent/patient advocates, participated in the sessions to provide their perspectives to the challenges confronting the physician/scientist and the implementation of cellular therapy clinical trials in pediatric diseases.

Speakers presented their clinical trial experiences in the following areas:

  • Allogeneic hematopoietic stem cell transplantation for congenital blood disorders
  • Autologous gene-modified hematopoietic stem cell transplantation for congenital blood disorders
  • Thymus transplantation for complete DiGeorge Anomaly
  • Allogeneic hematopoietic stem cell transplantation for metabolic and dermal diseases
  • Autologous gene-modified hematopoietic stem cell transplantation for a neurodegenerative, metabolic disease
  • Neural stem cell transplantation for a neurodegenerative disease
  • Autologous cord blood therapies for brain injuries
  • Transplantation of human embryonic stem cell derived progenitors for neural indications
  • Implantation of tissue engineered grafts

The three panel discussions were opened with statements by Amy Frohnmayer, a patient advocate for families afflicted with Fanconi Anemia; Tracy VanHoutan, a parent advocate for families afflicted with Batten Disease; and Tim Ringgold, a parent advocate for families afflicted with Epidermolysis Bullosa. The patient and parent advocates provided their perspective of clinical research for rare diseases and highlighted the importance of including all stakeholders for the development and conduct of successful cellular therapy clinical trials.

Dr. John Wagner concluded the workshop with a summary of the challenges and potential solutions to implementing and performing cellular therapy trials for pediatric diseases identified by the speakers, panelists and meeting participants.

Consensus and Recommendations

Common obstacles identified by investigators include:

  1. Most academic institutions lack the infrastructure required to support cell or gene therapy trials in pediatric populations. These needs vary from manufacturing capability to provide the experimental product to providing dedicated staff trained to implement and monitor clinical trials in a vulnerable population.
  2. There is little coordination between the multiple local review boards required to evaluate a trial, and this is further complicated by the review that takes place at a national level. Sometimes there are conflicting suggestions/requirements that cause many iterations to occur and uses up time and resources. As a result of the lengthy process, there may be a change in personnel on any of these review boards such that new questions arise with each resubmission.
  3. Many aspects of these studies do not fit the current federal funding paradigm with five years of funding and little flexibility in the carryover of funds. A major impediment is the length of time it takes to receive approval, and perform the required long-term follow-up of subjects to determine adverse effects on developmental parameters. A related issue is that many diseases under study are rare, leading to slow accrual. Another major impediment is that production of biological products is extremely expensive. Often, the manufacture process is long and/or cannot be performed ahead of time, precluding the availability of a preserved product following enrollment of the subject.


Appropriate federal agencies can work together to accomplish the following:

  • Development of disease specific centralized databases
  • Identification of centers of excellence or consortia with an established track record that in turn justifies longer term investment to conquer a given disease or set of diseases
  • Funding disease team working groups to develop appropriate efficacy and toxicity models and new functional readouts
  • Development of a ‘virtual’ home for pediatric cell and gene therapy and a funding mechanism that cuts across agencies or institutes
  • Increasing support for development of appropriate animal models which in some cases are lacking for specific disease/injury type to meet regulatory requirements
  • Increasing the research infrastructure, both mechanistically and regulatory, to support multi-institutional domestic and international trials for rare diseases
  • Explore research model(s) for joint development of clinical trials between academic centers and industry with adequate protection of trade secrets/proprietary information Investigators can work together to accomplish the following goals:
  • Work with patient advocacy groups to form partnerships in obtaining support and funding for research efforts to conquer a given disease or set of diseases
  • Generate trust among families, patients, their health care providers, and patient advocacy groups to promote participation in novel therapeutic clinical trials
  • Leverage cell-based therapies to expand indications to generate industry interest

NHLBI Contacts

Traci Heath Mondoro, PhD
Transfusion Medicine and Cellular Therapeutics Branch
Division of Blood Diseases and Resources

Lisbeth Welniak, PhD
Transfusion Medicine and Cellular Therapeutics Branch
Division of Blood Diseases and Resources

Workshop Planning Committee, Speakers and Panelists

  • Rosa Sanchez Rosen, MD, Blood Systems Research Institute, Chair
  • Robert Lindblad, MD, EMMES Corporation
  • Leslie Silberstein, MD, Children’s Hospital Boston
  • John E. Wagner, MD, University of Minnesota
  • Kenneth L. Berger, PhD, California Stem Cell, Inc.
  • Christopher Breuer, MD, Yale University
  • Charles S. Cox, Jr., MD, University of Texas – Houston
  • Lainie Friedman Ross, MD, PhD, University of Chicago
  • Amy Frohnmayer
  • John Hyde, MD, PhD, FDA
  • Hans-Peter Kiem, MD, FACP, Fred Hutchinson Cancer Research Center
  • Joanne Kurtzberg, MD, Duke University Medical Center
  • Jane S. Lebkowski, PhD, Geron Corporation
  • M. Louise Markert, MD, PhD, Duke University Medical Center
  • Paul J. Orchard, MD, University of Minnesota
  • Sung-Yun Pai, MD, Children’s Hospital Boston
  • Timothy Ringgold, Pioneering Unique Cures for Kids
  • John Scott, PhD, FDA/CBER/OBE/DB
  • Seema K. Shah, JD, National Institutes of Health
  • Robert D. Steiner, MD, Oregon Health & Science University
  • John F. Tisdale, MD, National Heart, Lung, and Blood Institute
  • Jakub Tolar, MD, PhD, University of Minnesota
  • Tracy Van Houtan, Noah’s Hope
  • Mark Walters, MD, Children’s Hospital & Research Center Oakland
  • David A. Williams, MD, Children’s Hospital Boston

Last Updated April 2012

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