Clinical Trials

This study will be a Phase I, open-label, non-randomized, dose-finding trial conducted at multiple clinical centers. The study is designed to determine the safety, tolerability and PK of TKM-080301 in adult patients with solid tumors or lymphomas that are refractory to standard therapy or for whom there is no standard therapy.

OBJECTIVES:

       -  Establish a biologic specimen repository (of tumor tissue, tissue arrays, lymphoblastoid cell lines, host DNA, tumor and host RNA, serum, and plasma) and database linked to clinical features and outcomes from well-characterized cohorts of children and young adults with Hodgkin's lymphoma.

       -  Provide specimens from diagnosis, early response evaluation, completion of chemotherapy and radiotherapy, long-term follow up, and relapse to study prognostic factors for early response, relapse, long-term outcomes, and identification of new biological targets for therapy.

     OUTLINE: This is a multicenter study.

     Patients enrolled on Hodgkin's lymphoma (HL) therapeutic clinical trials undergo collection of tumor tissue samples at baseline and at relapse or disease progression. Serum and anticoagulated peripheral blood samples are collected at baseline, at week 1, on day 1 of course 2, after completion of chemotherapy, after completion of radiotherapy, at 1 year after diagnosis, and at relapse or disease progression.

     Patients with relapsed or progressive disease who plan to enroll on HL relapse/retrieval clinical trials undergo collection of tumor tissue, serum, and anticoagulated peripheral blood samples at relapse or disease progression.

     Patients enrolled more than 1 year after completion of treatment undergo collection of tumor specimens, serum, and anticoagulated peripheral blood samples at time of clinical evaluation.

     PROJECTED ACCRUAL: A total of 1,272 patients will be accrued for this study.

The purpose of this study is to assess safety and efficacy of brentuximab vedotin in combination with bendamustine in patients with relapsed or refractory Hodgkin lymphoma. It is an open-label, 2-stage study designed to determine the recommended dose level of bendamustine in combination with brentuximab vedotin. The study will assess the safety profile of the combination treatment and determine what proportion of patients achieve a complete remission.

PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose of RAD001 and lenalidomide in subjects with relapsed/refractory Non-Hodgkin Lymphoma or Hodgkin Lymphoma. (Phase I) II. To assess tumor response to RAD001 and lenalidomide in subjects with relapsed/refractory Non-Hodgkin Lymphoma or Hodgkin Lymphoma. (Phase II) SECONDARY OBJECTIVES: I. To evaluate overall survival, progression-free survival, duration of response, and time to treatment failure of subjects receiving RAD001 and lenalidomide. II. To describe the adverse event profile (using CTCAE CTEP Active Version) of RAD001 and lenalidomide. OUTLINE: Patients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Ascenta Therapeutics, Inc. is conducting a clinical trial of the compound Debio 1143 (AT-406), a small molecule second mitochondria-derived activator of caspase C (Smac) mimetic.  In vivo and in vitro studies have demonstrated that Debio 1143 (AT-406) induces cell death in several tumor models by inhibiting XIAP (X linked IAP), cIAP-1 (cellular IAP-1) and cIAP-2 (cellular IAP-2), thus releasing initiator and effector caspases to promote apoptosis.  This protocol is a Phase I, dose-escalation, open-label, multi-center study conducted in patients with advanced solid tumors and lymphomas to evaluate the safety, tolerability and pharmacology of Debio 1143 (AT-406) in humans when administered orally.

PRIMARY OBJECTIVES: I. To determine the maximum tolerated doses (MTD) of LBH589 and RAD001 when used in combination in patients with myeloma or lymphoma (Phase I). II. Arm A: To evaluate the therapeutic activity of the combination of LBH589 with RAD001 in patients with relapsed or refractory lymphoma. (Phase II) III. Arm B: To evaluate the therapeutic activity of the combination of LBH589 with RAD001 in patients with relapsed or refractory multiple myeloma (Phase II) SECONDARY OBJECTIVES: I. To further describe the toxicities associated with the combination of LBH589 with RAD001 in each arm independently. II. To evaluate overall survival, progression-free survival, and duration of response in each arm independently. TERTIARY OBJECTIVES: I. To evaluate the pharmacokinetic interaction of LBH589 and RAD001. II. To assess the correlation between clinical (toxicity and/or tumor response or activity) effects with the pharmacologic (pharmacokinetic/pharmacodynamic) parameters, and/or biologic (correlative laboratory) results. OUTLINE: Patients receive oral panobinostat and oral everolimus once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed periodically for 2 years.