Clinical trial NCT03719898 (phase 2, status: withdrawn)
Conditions: anaplastic large cell lymphoma, alk-positive
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: brigatinib
SMILES: COC1=CC(=CC=C1NC1=NC=C(Cl)C(NC2=CC=CC=C2P(C)(C)=O)=N1)N1CCC(CC1)N1CCN(C)CC1
Reason stopped: 
    slow accrual
  
Eligibility criteria:

        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.

        Exclusion Criteria:

          1. History of another active primary malignancy within 2 years of initiating study
             treatment with the exception of non-melanomatous skin cancer, or any cancer that in
             the judgment of the investigator has been treated with curative intent and will not
             interfere with the study treatment plan and response assessment.

          2. Patients who have received chemotherapy or radiation therapy within 2 weeks of
             initiating study treatment.

          3. Patients may not be receiving any other investigational agents.

          4. Patients who have symptomatic CNS metastases (parenchymal or leptomeningeal) at
             screening or asymptomatic disease requiring an increasing dose of corticosteroids to
             control symptoms within 7 days prior to randomization.

             Note: If a patient has worsening neurological symptoms or signs due to CNS metastasis,
             the patient needs to complete local therapy and be neurologically stable (with no
             requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7
             days prior to enrollment.

          5. History of allergic reactions attributed to other ALK inhibitors

          6. History of interstitial pneumonitis or drug-related pneumonitis

          7. Impaired gastrointestinal function that may affect oral absorption of brigatinib

          8. Patients with known active Hepatitis B or Hepatitis C (defined as having a detectable
             hepatitis B or C viral load)

          9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements. Physician's discretion may be exercised to determine eligibility
             for patients with psychiatric illness/social situations.

         10. Pregnant or breast-feeding. Refer to section 4.4 for further detail.