FDA Approves Crizotinib for Children and Young Adults With Relapsed or Refractory, Systemic ALK-Positive Anaplastic Large Cell Lymphoma

January 15, 2021

On January 14, 2021, the U.S. Food and Drug Administration (FDA) approved crizotinib (Xalkori®) for pediatric patients aged one year or older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK) positive. The safety and efficacy of crizotinib have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL. 

FDA Approves Crizotinib for Children and Young Adults With Relapsed or Refractory, Systemic ALK-Positive Anaplastic Large Cell Lymphoma

Efficacy was evaluated in a multicenter, single-arm, open-label trial (Study ADVL0912; NCT00939770) of 26 patients aged 1–21 years with relapsed or refractory, systemic ALK-positive ALCL who had received at least one systemic treatment. Twenty patients received crizotinib 280 mg/morally twice daily and six patients received crizotinib 165 mg/m2 orally twice daily until disease progression or unacceptable toxicity. Patients were permitted to discontinue crizotinib to undergo hematopoietic stem cell transplantation.

Efficacy was based on objective response rate (ORR) and duration of response as assessed by an independent review committee. ORR in the 26 patients was 88% (95% CI = 71, 96), with a complete remission rate of 81%. Of the 23 patients who achieved a response, 39% maintained response for at least 6 months and 22% maintained response for at least 12 months.

Ocular toxicity (grade 1 or 2 visual disorders) occurred in 65% of patients with ALCL, gastrointestinal toxicity occurred in 92%, and serious adverse reactions occurred in 35%, most often from neutropenia and infection. The most common adverse reactions (≥ 35%), excluding laboratory abnormalities, were diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritus. Grade 3 or 4 laboratory abnormalities (≥ 15%) were neutropenia, lymphopenia, and thrombocytopenia.

The recommended crizotinib dosage for systemic ALCL is 280 mg/m2 orally twice daily based on body surface area. Antiemetics are recommended prior to and during treatment with crizotinib in patients with ALCL. Because of the risk of visual loss, ophthalmologic evaluations are recommended at baseline and serially thereafter, coupled with monthly assessments of visual acuity and visual symptoms.

View full prescribing information for crizotinib.

The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA granted the application priority review and breakthrough and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.   

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.         

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.    


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