ALK Phase 1 Clinical Trial Research

A pill designed to zero in on abnormal genes that drive specific cancers has produced encouraging early results in children with an uncommon but aggressive type of lymphoma, and in children with a rare form of neuroblastoma.

A phase 1 clinical trial of the drug crizotinib achieved remissions, with minimal side effects, for 10 of the children participating in a clinical study carried out by the multicenter Children’s Oncology Group (COG). Children’s Hospital of Philadelphia researcher Yael Mossé, MD, led the trial. It was the result of nearly two decades of work by collaborating researchers.

Studying ALK, a cancer-causing gene

Mossé previously led a team at CHOP that discovered in 2008 that mutations in the anaplastic lymphoma kinase (ALK) gene are present in 14 percent of cases of high-risk neuroblastoma, the most common solid cancer of early childhood. The same gene is disrupted in some cases of anaplastic large cell lymphoma (ALCL), a cancer of the lymph cells, and in patients with non-small-cell lung cancer.

Because drug manufacturers had already developed a drug called crizotinib for use in adult lung cancer clinical trials, Mossé and colleagues were able to quickly move crizotinib into an initial pediatric trial.

Results of the phase 1 trial

The trial was not restricted to patients with known ALK abnormalities, but was open to children with certain refractory or relapsed cancers. Side effects were minimal, even though many of the dosages were relatively high.

Anaplastic large cell lymphoma

Eight children with anaplastic large cell lymphoma (ALCL) were enrolled in the trial.

  • 7 of the 8 had complete responses — no cancer could be detected with imaging scans. Read Zach's lymphoma story.
  • These children's symptoms began to disappear within days of taking the medication.


Twenty-seven patients enrolled in the trial had neuroblastoma, a difficult-to-treat cancer of the nervous system.

  • Of the two patients with known ALK mutations occurring in every cell in their body, which can be found in the very rare familial neuroblastoma, one achieved a complete remission. Watch Edie's neuroblastoma story.
  • Of the 19 neuroblastoma patients in the trial whose ALK status was not able to be studied in the molecular diagnostic lab at CHOP, a second patient had a complete remission.

What this means for families

For children with an uncommon form of lymphoma, anaplastic large cell lymphoma (ALCL), we've learned that changes in the ALK gene is likely what fuels their cancer. Thus, for children with relapsed ALCL, crizotinib may offer benefit, and additional studies in larger groups of children will soon follow.

In neuroblastoma, we do not yet know whether crizotinib will prove to be an advance in treatment. For children with relapsed neuroblastoma, additional testing may allow for children with a rare and very specific type of neuroblastoma to participate in ongoing clinical trials within the Children’s Oncology Group.

Diagnostic tests for children with neuroblastoma

CHOP's molecular genetics lab currently offers testing for the ALK mutation to families across the country. Having this information provides potentially more treatment options for children who have suffered a relapse, with the ultimate goal of customizing the approach when patients are newly diagnosed with the type of neuroblastoma that has an ALK abnormality.

Learn more about these tests and how to submit a specimen:

  • Neuroblastoma (ALK and PHOX2B Sequencing Panel)
  • Neuroblastoma (ALK Known Mutation)
  • Neuroblastoma (ALK Sequence Analysis)
  • Neuroblastoma / Classic Congenital Central Hypoventilation Syndrome, CCHS (PHOX2B Gene Sequence Analysis)
  • Neuroblastoma / Classic Congenital Central Hypoventilation Syndrome, CCHS (PHOX2B Known Mutation)

All specimens submitted for testing require a Molecular Genetics Requisition Form and Molecular Genetics Informed Consent.

If you have any questions about these diagnostic tests, please contact Avni Santani, PhD, scientific director of the Molecular Genetics Laboratory, at 267-426-5535.

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