KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma (KPT-330+RICE)
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|ClinicalTrials.gov Identifier: NCT02471911|
Recruitment Status : Recruiting
First Posted : June 15, 2015
Last Update Posted : January 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-Cell Lymphoma||Drug: KPT-330 Drug: Rituximab Drug: Etoposide Drug: Carboplatin Drug: Ifosfamide Drug: Dexamethasone||Phase 1|
Although aggressive B-cell lymphomas are potentially curable with front-line chemotherapy, at least one-third of patients experience progression or relapse. Second-line regimens such as rituximab, ifosfamide, carboplatin, and etoposide (RICE) are administered with the goal of cytoreduction prior to autologous stem cell transplantation (ASCT) in eligible patients. However, half of patients who receive salvage treatment and ASCT are still not cured.
Selinexor is a Selective Inhibitor of Nuclear Export / SINE compound, which is a new class of molecule. SINE compounds have been shown to induce apoptotic cell death in pre-clinical models of AML, CLL, T-ALL, and Ph+ ALL as well as B and T-cell non-Hodgkin lymphomas. Preliminarily, selinexor has demonstrated promising single-agent clinical activity in patients with previously treated NHL including DLBCL, warranting further investigation. Based on promising preclinical and clinical data, selinexor is currently under evaluation in combination with chemotherapy for solid tumors.
The investigators hypothesize that the combination of selinexor plus RICE will be well-tolerated and clinically active in participants with previously treated aggressive B-cell lymphomas and propose a phase I trial to evaluate this combination. Moreover, Investigators will evaluate primary patient samples before and after selinexor to investigate the mechanisms of action of selinexor, including the mechanisms by which selinexor sensitizes cells to chemotherapy, and evaluate other novel drug combinations in aggressive B-cell lymphomas.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Investigator-Initiated Study of Selinexor (KPT-330) Plus RICE in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas|
|Study Start Date :||November 2015|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||June 2020|
Experimental: All subjects
All subjects will receive KPT-330 (selinexor) on days -5 and -3 starting one week before RICE chemotherapy is started. Once chemotherapy starts, selinexor will be given on days 1, 3, and 5 of each chemotherapy cycle.
RICE chemotherapy will consist of Rituximab, ifosfamide, carboplatin, etoposide, and dexamethasone.
KPT-330 administered orally on days -5 and -3 prior to starting chemotherapy. Once chemotherapy starts, KPT-330 will be administered on days 1, 3, and 5 of each cycle. Dose levels will range from 20 mg to 100mg with a standard 3+3 escalation schema.
Other Name: SelinexorDrug: Rituximab
IV Rituximab 375 mg/m2 on D1
Other Name: RituxanDrug: Etoposide
IV Etoposide 100 mg/m2 on D1-3Drug: Carboplatin
IV Carboplatin AUC 5 on D2Drug: Ifosfamide
IV Ifosfamide 5 g/m2 on D2Drug: Dexamethasone
20 mg qd on Days -5 and -3. 20 mg qd on Days 1-5
- Maximum Tolerated Dosage (MTD) of Selinexor/KPT-330 when combined with RICE chemo in a relapsed/refractory aggressive b-cell lymphoma setting. [ Time Frame: approximately 24 months ]The highest dose level at which no more than 1 or 6 patients presents with a dose-limiting toxicity (DLT) during the first 6 cycles of treatment
- Survival of subjects treated with KPT-330 + RICE [ Time Frame: approximately 24 months per patient ]Overall survival of patients enrolled on KPT-330 + RICE
- Progression-Free Survival of subjects treated with KPT-330 + RICE [ Time Frame: approximately 24 months per patient ]Progression-free survival of patients enrolled on KPT-330+RICE
- Number of patients who demonstrate a Response to KPT-330+RICE [ Time Frame: approximately 24 months per patient ]The efficacy (as assessed by clinical response) of the combination of KPT-330 + RICE in patients with Rel/Ref b-cell lymphoma
- Number of patients who undergo stem cell collection after induction therapy with KPT-330 + RICE [ Time Frame: approximately 24 months per patient ]The number of patients who can feasibly undergo a stem cell transplant after treatment with KPT-330+RICE
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471911
|Contact: Amelyn Rodriguez, RN||(212) email@example.com|
|Contact: Rita Gazivoda, RNfirstname.lastname@example.org|
|United States, New York|
|Weill Cornell Medical College||Recruiting|
|New York, New York, United States, 10021|
|Contact: Amelyn Rodriguez, RN 212-746-1362|
|Contact: Rita Gazivoda, RN 212-746-0702|
|Principal Investigator:||Peter Martin, MD||Weill Medical College of Cornell University|