KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
Condition: Adult T-cell Leukemia-Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell
Intervention: KW-0761; Pralatrexate; gemcitabine plus oxaliplatin; DHAP
Intervention description: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression; 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression; gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression; dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression
Intervention MeSH terms: Gemcitabine; Oxaliplatin; Mogamulizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adult T cell Leukemia-Lymphoma (ATL)

Summary:

      The purpose of this study is to estimate the overall response rate of subjects with relapsed
      or refractory Adult T-cell Leukemia-Lymphoma (ATL).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and female subjects ≥ 18 years of age

          -  Confirmed diagnosis of ATL (excluding smoldering subtype)

          -  Subjects must currently have evidence of disease in at least one of the following:

               -  Lymph nodes

               -  Extranodal masses

               -  Spleen or liver

               -  Skin

               -  Peripheral blood

               -  Bone marrow

          -  Relapsed or refractory after at least one prior systemic therapy regimen for ATL;

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study
             entry

          -  Resolution of all clinically significant toxic effects of prior cancer therapy to
             grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse
             Events, version 4.0 (NCI-CTCAE, v.4.0)

          -  Adequate hematological, hepatic and renal function

        Exclusion Criteria:

          -  Smoldering subtype of ATL;

          -  Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who
             has not achieved a response (CR or PR) or maintained stable disease for at least 12
             weeks on last immediate prior therapy;

          -  History of allogeneic transplant;

          -  Autologous hematopoietic stem cell transplant within 90 days of study entry;

          -  Untreated human immunodeficiency virus (HIV)

          -  Has known hepatitis C. Patients who are hepatitis C antibody positive but are
             hepatitis C quantitative PCR negative may be enrolled;

          -  Has hepatitis B based on PCR testing for hepatitis B virus DNA. Patients who are
             hepatitis B core antibody positive but PCR negative may be enrolled if placed on
             appropriate anti-hepatitis B virus prophylaxis prior to commencing treatment with
             KW-0761. Patients who are hepatitis B core antibody positive based on prior
             vaccination need not receive prophylaxis;

          -  Have had a malignancy in the past two years except non-melanoma skin cancers, melanoma
             in situ, localized cancer of the prostate with current PSA < 0.1 µg/mL, treated
             thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of
             the breast who is currently without evidence of disease;

          -  Clinical evidence of central nervous system (CNS) involvement or metastasis. In
             subjects suspected of having CNS disease, an MRI of the brain and/or lumbar puncture
             should be done to confirm;

          -  Psychiatric illness, disability or social situation that would compromise the
             subject's safety or ability to provide consent, or limit compliance with study
             requirements;

          -  Significant uncontrolled intercurrent illness

          -  Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;

          -  Known active autoimmune diseases will be excluded (For example; Grave's disease;
             systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);

          -  Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.

          -  Prior treatment with KW-0761;

          -  Initiation of treatment with systemic corticosteroids while on study is only permitted
             for acute and brief complications of underlying disease (e.g., hypercalcemia) or for
             treatment related side effects (e.g., including pre-medication for infusion reaction,
             nausea and vomiting). Subjects on systemic corticosteroids prior to enrollment must be
             off for 7 days before initiation of study treatment, unless specifically indicated for
             the treatment of hypercalcemia. (subjects may receive inhalation corticosteroids and
             replacement doses of systemic corticosteroids as needed);

          -  Initiation of treatment with topical corticosteroids while on study is not permitted
             except to treat an acute rash. Subjects on a stable dose of medium or low potency
             topical corticosteroids for at least 4 weeks prior to Pre-treatment Visit may continue
             use at the same dose, although the investigator should attempt to taper the use to
             lowest dose tolerable;

          -  Have had interferon-α and/or zidovudine within 1 week, or anti-neoplastic
             chemotherapy, radiation, immunotherapy, or investigational medications within 2 weeks
             of first study treatment;

          -  Subjects on any immunomodulatory drug. Subjects on any immunomodulatory drug within 4
             weeks of their first dose of KW-0761 are also excluded.