Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma

Inclusion Criteria

• •1. Patients must have a histologically confirmed diagnosis of relapsed or refractory ALCL with documented ALK+ status
• •2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIL 2017 criteria as described in detail in section 11.0
• •3. Ongoing toxicities from prior therapy must be resolved to ≤ grade 1 (with the exceptions of grade 2 peripheral neuropathy and/or alopecia). Patients with existing toxicities that are non-significant even though greater than grade 1 can be enrolled after discussion with the sponsor-investigator.
• •4. Age \> 18 years.
• •5. ECOG performance status 0-2
• •6. Prior use of ALK inhibitors aside from brigatinib is permitted but 8 patients enrolled need to be ALK inhibitor treatment naive
• •7. Patients with no archival tissue available must be agreeable to fresh biopsy at baseline.
• •8. Patients with a known history of HIV are permitted provided the CD4 count ≥ 100 cells/µL and serum HIV viral load \< 50 copies/mL. Patients must be on stable combination antiretroviral therapy at the time of treatment initiation.
• •9. Patients must have normal organ and marrow function as defined below
• •* Absolute neutrophil count \> 1,000/mcL
• •* Platelets \> 75,000/mcL (or 50,000/mcL if known bone marrow involvement by lymphoma)
• •* Total bilirubin within normal institutional limits (up to 2x ULN if history of Gilbert's syndrome or known liver involvement)
• •* AST/ALT (SGOT/SGPT) \< 2 times institutional normal limits
• •* Creatinine within 1.5 x upper limit of normal institutional limits OR
• •* Creatinine clearance \> 30 ml/min/1.73 m2 for patients with creatinine levels above 1.5x upper institutional normal
• •* Serum lipase/amylase ≤1.5 × ULN
• •* Hemoglobin ≥10 g/dL (can be transfused to achieve Hgb ≥10 g/dL)
• •10. Ability to understand and willingness to sign a written informed consent and HIPAA consent document. LARs are allowed to sign on patient's behalf with proper documentation.
• •11. Female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile. Female patients of childbearing potential should agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
• •12. Male patients, even if surgically sterilized (i.e., status post-vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug.