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Acute Myeloid Leukemia: Developing Drugs and Biological Products for Treatment: Guidance for Industry; Availability

FinalOncology Center of Excellence Center for Drug Evaluation and Research Center for Biologics Evaluation and Research10/17/2022

Description

The purpose of this guidance is to assist sponsors in the clinical development of drugs and biological products for the treatment of acute myeloid leukemia (AML). Specifically, this guidance addresses FDA’s current thinking regarding the overall development program and clinical trial designs for the development of drugs to support an indication of treatment of AML, including indications limited to an individual phase of treatment (e.g., maintenance, transplantation preparative regimen, etc.).

Scope & Applicability

Product Classes

5
Biological Products

Requires analytical comparability per ICH Q5E

CAR T Cells

DLT criteria for chimeric antigen receptor T cells

Gene Therapy

A type of ATMP involving recombinant nucleic acids or viral vectors.

Cellular therapy products

sponsors should consult specific guidances for these products

Gene therapy products

sponsors should consult specific guidances for these products

Stakeholders

3
Sponsor

Entity responsible for submitting applications under section 524B

Healthy volunteers

Possible to conduct the FIH trial in healthy volunteers

Investigator

Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining

Regulatory Context

Attributes

10
Orphan designation

Status that does not exempt a drug from pediatric investigation requirements under certain conditions.

Platelet transfusion dependence

Baseline status for transfusion independence assessment.

RBC transfusion dependence

Baseline status for transfusion independence assessment.

Marrow blasts percentage

Marrow blasts percentage used for CR response

Nonintensive therapies

Lower doses of cytotoxic chemotherapy or targeted drugs with limited organ toxicities.

Intensive therapies

Regimens expected to cause high-grade organ toxicity or prolonged neutropenia.

Benefit-risk ratio

Durable CR support for approval depends on the benefit-risk ratio.

Event-Free Survival

Efficacy endpoint (EFS)

Overall Survival

Efficacy endpoint (OS)

Dose-Limiting Toxicity

DLT criteria for trial safety

Identified Hazards

Hazards

1
Cytokine release syndrome

A toxicity (CRS) associated with CAR T cells.

Related CFR Sections (2)

See Also (8)