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CRISP (tumors with ALK/MET/ROS1 abnormalities)

Clinical study of the safety and efficacy of the drug crizotinib in children, either alone or in combination with other drugs.
Who can enter
  • Children with anaplastic large cell lymphoma (ALCL), neuroblastoma (NB), rhabdomyosarcoma (RMS), inflammatory myofibroblastic tumor (IMT) or another tumor in which an abnormality has been detected in the ALK, MET or ROS1 gene, and in whom the disease has returned (relapsed) or reacted insufficiently to treatment (refractory)
  • Age: 1-21 years


The goal of this study is to determine a safe dose of the drug crizotinib when given alone, and when given in combination with temsirolimus. In addition, we want to find out how the children respond to the treatment, and what side effects the treatment may cause.


Changes in the ALK gene occur in almost all cases of anaplastic large cell lymphoma (ALCL). These abnormalities lead to enhanced growth of tumor cells. Crizotinib is not chemotherapy, but a so-called tyrosine kinase inhibitor. It is a drug that specifically targets ALK, thus inhibiting tumor cell growth. It also has activity against MET and ROS1, genes that resemble ALK. Abnormalities in ALK, MET and ROS1 are found in other tumors as well, among which neuroblastoma, rhabdomyosarcoma, and inflammatory myofibroblastic tumor (IMT).

There are strong indications that crizotinib can help slow down tumor growth. For example, in a study in the United States 26 children with ALCL were treated with crizotinib, of which 21 reached complete remission, two reached partial remission and three remained stable. Overall, crizotinib was well tolerated. Crizotinib has been approved by the European and American health authorities (EMA and FDA) for the treatment of adults with lung cancer carrying an ALK abnormality.

We will perform this study in three groups of children:

  • Stratum 1b: crizotinib alone in ALCL
  • Stratum 2: crizotinib + temsirolimus in neuroblastoma and rhabdomyosarcoma
  • Stratum 3: crizotinib alone in IMT and other tumors with ALK/MET/ROS1 abnormalities

The drug temsirolimus has been approved for the treatment of kidney cancer and a certain type of lymphoma in adults. It has been studied in children before; also in children with neuroblastoma or rhabdomyosarcoma. For neuroblastoma we know that a tumor carrying an ALK abnormality often responds insufficiently to the drug crizotinib alone. In patients with neuroblastoma and rhabdomyosarcoma we expect that temsirolimus may make the tumor more sensitive to crizotinib.

The combination of crizotinib with temsirolimus has not been studied before.

In children with IMT the tumor is sometimes located in a difficult spot or is too large to be removed completely by surgery. In these children we want to see if treatment with crizotinib helps to reduce the tumor size. Hopefully the tumor can then be removed completely. In children with other tumors carrying an ALK/MET/ROS1 abnormality we hope that crizotinib will help control the disease.

In order to participate in a study please refer to your/your child’s doctor.
For international patients: please feel welcome to contact our International Office.

Last reviewed

September 2, 2022