This phase I/II trial studies the side effects and best dose of lenalidomide when given together with high-dose chemotherapy (vorinostat, gemcitabine hydrochloride, busulfan, and melphalan) followed by stem cell transplant and to see how well the regimen works in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to treatment (refractory), and is of the activated B-cell-like (ABC) subtype. Lenalidomide may stimulate the immune system to attack cancer cells. Drugs used in chemotherapy, such as vorinostat, gemcitabine hydrochloride, busulfan, and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combining lenalidomide with this chemotherapy regimen may be an effective treatment for the ABC subtype of diffuse large B-cell lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02589145.
PRIMARY OBJECTIVES:
I. Establish the maximum tolerated dose (MTD) of lenalidomide combined with vorinostat/gemcitabine (gemcitabine hydrochloride)/busulfan/melphalan with autologous stem-cell transplant (ASCT).
II. Determine 2-year event-free survival (EFS).
SECONDARY OBJECTIVES:
I. Assess 2-year overall survival (OS).
II. Determine complete remission (CR) rate.
III. Determine overall remission rate (ORR).
IV. Describe the toxicity profile.
V. Evaluate interferon regulatory factor 4 (IRF4), spi-B transcription factor (Spi-1/PU.1 related) (SPIB), signal transducer and activator of transcription 1 (STAT1), phosphorylated (p)-STAT1, caspase recruitment domain family member 11 (CARD11), I-kappa-kinase-beta and p-I-kappa-kinase-beta in peripheral blood mononuclear cells (PBMNC) pre- and post-treatment (at baseline and on day -1).
OUTLINE: This is a phase I, dose-escalation study of lenalidomide, followed by a phase II study.
Patients receive vorinostat orally (PO) and lenalidomide PO on days -9 to -2, within 1 hour before chemotherapy. Patients then receive gemcitabine hydrochloride intravenously (IV) over 4.5 hours on days -8 and -3, busulfan IV over 2 hours on days -8 to -5, and melphalan IV over 30 minutes on days -3 and -2. Patients with cluster of differentiation (CD)20-positive lymphoma also receive rituximab IV over 3-6 hours on day -9. All patients undergo autologous peripheral blood progenitor cell (PBPC) transplant on day 0.
After completion of study treatment, patients are followed up at 100 days.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorYago L. Nieto
