Phase II Trial of the Aurora Kinase A Inhibitor, MLN8237, in Peripheral T-Cell Non-Hodgkin Lymphoma

Patients must have histologically or cytologically confirmed relapsed/refractory non-Hodgkin lymphoma (NHL) having progressed after a minimum of one systemic therapy with any of the following T-cell histologies: Peripheral T-cell NHL not other wise specified (PTCL, nos), Anaplastic large cell T-cell lymphoma (ALCL) both Anaplastic lymphoma kinase either positive or negative, Angioimmunoblastic T-cell NHL, Subcutaneous panniculitis like T-cell lymphoma, Enteropathy associated T-cell NHL, Hepatosplenic T-cell lymphomas, Extranodal NK/T-cell lymphoma, nasal type, Adult T-cell leukemia/lymphoma, Unclassifiable PTCL, Transformed cutaneous T-cell lymphoma (CTCL) to PTCL with systemic
involvement (not local skin transformation)
No other histologies are eligible. Examples of ineligible histologies include: T-cell
prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, NK cell leukemia,
mycosis fungoides, Sezary syndrome, lymphomatoid papulosis, and primary cutaneous T-cell lymphoma. Patients must have received at least one course of prior systemic therapy which may include chemotherapy, antibody therapy, or immunotherapy. Patients must not be within
42 days of antibody treatment including alemtuzumab or within 84 days of
radioimmunotherapy. For all other forms of systemic therapy, patients must have
completed therapy at least 21 days prior to registration. Steroids at a low dose for control
of itching (up to the equivalent of 20 mg of prednisone daily) are allowed. Patients may have received prior radiation in combination with systemic therapy. Patients must not be within 21 days of external beam radiation therapy. Patients must not have received a previous allogeneic stem cell transplant or be within 90 days of an autologous stem cell transplant. Pathology Review: Adequate sections or a paraffin block from the relapsed/refractory specimen must be submitted for review by the lymphoma pathology group. Patients must have bidimensionally measurable disease within
28 days prior to registration. A diagnostic quality CT scan of the chest abdomen, pelvis,
neck and PET/CT must be performed within 28 days of registration. Patients who also have non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration. Patients must have a bilateral or unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration. Patients must not have clinical evidence of central nervous system involvement by lymphoma. Any laboratory tests that are performed to assess clinical signs of central nervous system involvement must have been performed within 42 days prior to registration, and the results must be negative. Patients must be able to swallow tablets. Patients must be ≥ 18 years of age. Patients known to be HIV-positive must not have multi-drug resistant HIV infection, CD4
counts < 150/mcL or other concurrent AIDS-defining conditions. Patients must have absolute granulocyte count ≥ 1,500 cells/mcL and platelet count ≥75,000 cells/mcL measured within 14 days prior to registration. Patients with documented marrow involvement may be transfused to this value.
Patients must have adequate kidney function as evidenced by at least ONE of the
following:
� Serum creatinine (mg/dL) ≤ IULN obtained within 14 days prior to registration.
� Calculated creatinine clearance > 50 ml/min. The serum creatinine value used in
the calculation must have been obtained within 14 days prior to registration.
Calculated creatinine clearance =
(140-age) x wt (kg) x [0.85 (if female)]
72 x creatinine (mg/dL)
Patients must have a serum bilirubin ≤ 2 x institutional upper limit of normal within 14
days prior to registration. Patients must have serum AST and ALT both ≤ 2.5 x IULN obtained within 14 days prior to registration.
Patients must have serum LDH obtained within 14 days prior to registration. Patients must have a Zubrod performance status of 0, 1 or 2 (see Section 10.4). Patients must NOT have NYHA Class II � IV heart failure. No other prior malignancy is allowed except for the following: adequately treated basal
cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from
which the patient has been disease free for five years. The effects of MLN8327 on the developing human fetus are unknown. For this reason and because aurora kinase A inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, pregnant or nursing women are not eligible.
Women/men of reproductive potential must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation and for 4 months after completion of MLN8237
administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician
immediately.