ANHL12P1

Principal Investigator: Phillip Barnette
Keywords: Pediatrics , Oncology , Anaplastic Large Cell Lymphoma , ALCL Department: Pediatric Administration
IRB Number: 00070168 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

The main goals of this study are:

  • To find out what effects, good and/or bad, crizotinib, in combination with standard chemotherapy, has on people with ALCL.
  • To find out what effects, good and/or bad, brentuximab vedotin, in combination with standard chemotherapy, has on people with ALCL.

 

Another goal of the study is to see how a person’s disease is responding to treatment. If we know how a person’s disease is responding to treatment, then we hope we will have a better understanding of how likely it is that the cancer will come back.

 

Detailed Description

Many children with ALCL can be cured with current treatments, but treatments do not always stop the cancer from coming back. We are testing experimental drug combinations by adding brentuximab vedotin or crizotinib to standard chemotherapy in the hopes of finding a more effective treatment for ALCL. Brentuximab vedotin (previously known as SGN-35) has been approved by the FDA for the treatment of subjects with Hodgkins lymphoma and subjects with ALCL when other treatments have been tried and are no longer working. It has been shown to be well-tolerated without a lot of side effects in adults. For this study, brentuximab vedotin is an experimental drug because it has not been given with other chemotherapy at the same time in children with ALCL. Brentuximab vedotin is a drug known as an antibody-drug conjugate (ADC) which means it is a combination of two parts. The first part is an antibody (a man-made version of an immune system protein) that finds a protein called “CD30” found on the surface of most the lymphoma (cancer) cells. The second part is a chemotherapy (anti-cancer) drug that stops the cancer cell from dividing (which gets rid of it). Brentuximab vedotin uses the antibody part to find the cancer cells and then kills the cancer cell with the chemotherapy part. A major cause of ALCL is thought to be the expression of a protein called Anaplastic Lymphoma Kinase (ALK). Crizotinib is a drug which works directly on ALK to kill the cancer cell. Crizotinib has been shown to work against ALCL in a small number of patients after other treatments have not worked. Crizotinib is considered an experimental drug because it has not been given with other chemotherapy at the same time in children with ALCL. We are using crizotinib because it potentially targets one of the main causes of ALCL. But there is a lot that we do not know about crizotinib yet.

Inclusion Criteria

  • Patients must be less than 22 years of age at the time of study enrollment
  • Patients must be newly diagnosed with histologically proven ALCL.  Disease must be CD30 positive, ALK positive, and patients must have Stage II, III, or IV disease.
  • Patients must be expected to live at least 8 weeks or more
  • Previous steroids and/or radiation for emergent management of mediastinal mass will be allowed
  • Intrathecal chemotherapy prior to enrollment will be allowed for the current diagnosis of ALCL as long as CSF is obtained prior and is negative for ALCL.
  • Patients must have adequate organ function as defined in the protocol

Exclusion Criteria

  • Patients with CNS disease
  • Patients with disease limited to the skin
  • Patients with Stage I disease
  • Patient who have received any prior cytotoxic chemotherapy for the current diagnosis of ALCL or any cancer diagnosed previously are not eligible except as stated in protocol (clarified with Amendment 2 to state that intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of ALCL as long as adequate CSF is obtained prior to administration of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL.)
  • Pregnancy or breastfeeding
  • Sexually active patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of treatment and for 3 months after stopping treatment
  • Patients with Down syndrome are not eligible due to the amount of methotrexate and potential for side effects
  • Patients with an immunodeficiency that existed prior to diagnosis such as primary immunodeficiency syndromes, HIV or organ transplant recipients  (Note: Patients with HIV will be considered at a later date)
  • Patients who weigh less than 10kg
  • CYP3A4 Substrates with Narrow Therapeutic Indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible.
  • CYP3A4 Inhibitors: Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin, many NNRTIs, diltiazem, verapamil, and grapefruit juice are not eligible. See Appendix III of protocol.
  • CYP3A4 Inducers: Patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John’s wort are not eligible. See Appendix III of protocol.

Clarified with Amendment 2:

Previous steroid treatment and/or radiation treatment is not allowed unless it is for the emergent management of a mediastinal mass. Emergent steroid treatment and/or radiation should stop once protocol therapy is initiated.