Study title: Intensified Methotrexate, Nelarabine (Compound 506U78; IND # 52611) and Augmented BFM Therapy for Children and Young Adults with Newly Diagnosed T- Cell Acute Lymphoblastic Leukemia (hereinafter “AALL0434”)

Dear Mr. Hodgson,

The Office for Human Research Protections (OHRP) is unable to substantiate the allegations lodged against the Children’s Hospital of Philadelphia (CHOP) Human Research Protections Program (HRPP) and makes no determination of noncompliance with the U.S. Department of Health and Human Services (HHS) regulations for the protection of human research subjects.

Background: In February 2016, OHRP received allegations of CHOP’s noncompliance with HHS regulations for the protection of human research subjects (Subpart A, 45 CFR part 46) with respect to AALL0434. It is our understanding that AALL0434 was initiated prior to January 21, 2019, and is subject to the Common Rule as it existed at that time (the “Pre-2018 Requirements”). Therefore, the regulatory citations in this letter refer to the Pre-2018 Requirements.

The complainant alleged that for the above referenced study:

• The informed consent did not adequately describe the risks of the research nor disclose appropriate alternative courses of treatment per 45 CFR 46.116(a)(2) and (4) requirements.
• The research team pressured a child and her family to remain in the study in contravention of 45 CFR 46.116(a)(8) requirements.
• Risks to subjects in the study were not minimized per research approval criterion at 45 CFR 46.111(a)(1).

OHRP reviewed CHOP’s investigation report, versions of the study protocol for the period associated with these allegations, the informed consent forms, IRB records for this study, and documents provided by the complainant.

Based on our review of these materials, OHRP did not find evidence to support the allegations of noncompliance with HHS regulations for the protection of human subjects.

This investigation is closed. We appreciate your institution’s continued commitment to the protection of human research participants. Please feel free to contact me if you have any questions.

Sincerely,

Lisa Buchanan, MAOM, CIP
Director, Division of Compliance Oversight

CC (email only):
Ms. Amy Schwarzhoff, MS, MBA, Human Protection Administrator, Children’s Hospital of Philadelphia
Ms. Winifred Meeker-O’Connell, Director, Office of Clinical Policy, Food and Drug Administration (FDA)
Dr. Michelle Bulls, Director, OPERA, Office of Extramural Research, National Institutes of Health (NIH)
Dr. Pamela Kearney, Director, Division of Human Subjects Research, Office of Extramural Research, NIH
Dr. Adam Berger, Director, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Ms. Lydia Kline, Team Lead, Clinical Research Policy, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Center for Devices and Radiological Health (CDRH) IRB: BIMO-CDRH@fda.hhs.gov
Center for Biologics Evaluation and Research (CBER): CBERBIMONotification@fda.hhs.gov
Office of Regulatory Affairs (ORA): orabimoinspectionpoc@fda.hhs.gov
Center for Drug Evaluation and Research (CDER): BIMO-CDEROSI@fda.hhs.gov