Safety and Efficacy Study of PLX3397 in Adults With Relapsed or Refractory Hodgkin Lymphoma
Condition: Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: PLX3397
Intervention description: Capsules administered once or twice daily, continuous dosing. Subjects will begin with 900 mg/day, but should safety data allow in our PLX108-01 study, subject may dose at 1200 mg/day.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hodgkin Lymphoma

Summary:

      PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity.The primary
      objective of this study is to evaluate the efficacy, as measured by overall response rate, of
      orally administered PLX3397 in patients with relapsed or refractory classical Hodgkin
      lymphoma (HL). Secondary objectives include safety, the duration of response, the disease
      control rate, progression free survival, and how the drug affects your body.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients ≥18 years old

          2. Pathologic confirmation of relapsed or refractory classical Hodgkin lymphoma, with
             archival or fresh tissue available for retrospective analysis.

          3. Patients must have progressed after-or been ineligible for-autologous stem cell
             transplantation. Patients who received a prior allogeneic stem cell transplantation
             are eligible if they have no evidence of graft versus host disease (GVHD) and have
             been off immunosuppression for at least 3 months prior to Cycle 1 Day 1 (C1D1).

          4. Documented disease that is radiographically measurable (≥2 cm in the largest
             transverse dimension).

          5. Patients must have discontinued any previous monoclonal antibody, radioimmunotherapy,
             or cytotoxic chemotherapy at least 28 days prior to C1D1 and must have recovered fully
             from the side effects of that treatment prior to beginning study treatment.

          6. Women of child-bearing potential must have a negative pregnancy test within 7 days of
             initiation of dosing and must agree to use an acceptable method of birth control while
             on study drug and for 3 months after the last dose. Women of non-childbearing
             potential may be included if they are either surgically sterile or have been
             postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an
             acceptable method of birth control while on study drug.

          7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          8. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x
             109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, Aspartate Transaminase (AST) / Alanine
             Transaminase (ALT) ≤2.5x Upper limit of normal (ULN), creatinine ≤1.5x ULN)

          9. Willing and able to provide written informed consent prior to any study related
             procedures and to comply with all study requirements

        Exclusion Criteria:

          1. Investigational drug use within 28 days of the first dose of PLX3397

          2. History or clinical evidence of central nervous system, meningeal, or epidural disease
             including brain metastasis

          3. Patients with another active cancer [excluding basal cell carcinoma or cervical
             intraepithelial neoplasia (cervical carcinoma in situ) or melanoma in situ]. Prior
             history of other cancer is allowed, as long as there was no active disease within the
             prior 5 years.

          4. Patients with uncontrolled intercurrent illness, an active or uncontrolled infection,
             or a fever >38.5˚C (not due to tumor fever) on C1D1

          5. Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel
             resection that would preclude adequate absorption

          6. Patients with serious illnesses, medical conditions, or other medical history
             including abnormal laboratory results, which in the investigator's opinion would be
             likely to interfere with a patient's participation in the study, or with the
             interpretation of the results

          7. Women of child-bearing potential who are pregnant or breast feeding

          8. Corrected QT interval (QTc) ≥450 msec.