Olaparib and High-Dose Chemotherapy in Treating Participants With Relapsed or Refractory Lymphomas Undergoing Stem Cell Transplant
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|ClinicalTrials.gov Identifier: NCT03259503|
Recruitment Status : Recruiting
First Posted : August 23, 2017
Last Update Posted : September 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Diffuse Large B-Cell Lymphoma Recurrent T-Cell Non-Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Hodgkin Lymphoma Refractory T-Cell Non-Hodgkin Lymphoma||Drug: Busulfan Drug: Gemcitabine Drug: Melphalan Drug: Olaparib Procedure: Peripheral Blood Stem Cell Transplantation Other: Pharmacokinetic Study Biological: Rituximab Drug: Vorinostat||Phase 1|
I. Establish the maximum tolerated dose (MTD) of olaparib combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant [ASCT]).
I. Determine the 2-year event-free survival (EFS). II. 2-year overall survival (OS). III. Complete remission (CR) rate. IV. Overall remission rate (ORR). V. Describe the toxicity profile. VI. Describe changes of deoxyribonucleic acid (DNA) damage response and repair, poly(ADP-ribose) polymerase (PARP) inhibition and downstream cellular effects in peripheral blood mononuclear cells and, when available, malignant lymphocytes obtained by fine needle aspiration (FNA) of peripheral lymph nodes.
OUTLINE: This is a dose-escalation study of olaparib.
Participants receive olaparib orally (PO) twice daily (BID) on days -11 to -3, vorinostat PO on days -10 to -3, gemcitabine intravenously (IV) over 4.5 hours on days -9 and -4, busulfan IV over 3 hours on day -9 to -6, melphalan IV over 30 minutes on days -4 and -3, and undergo peripheral blood stem cell transplant IV over 30-60 minutes on day 0. Patients with CD20+ tumors also receive rituximab IV over 3-6 hours on day -10.
After completion of study treatment, participants are followed up every 1-2 days for 30 days and then every 2 weeks for up to 100 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Olaparib Combined With High-Dose Chemotherapy for Refractory Lymphomas|
|Actual Study Start Date :||September 10, 2019|
|Estimated Primary Completion Date :||July 1, 2023|
|Estimated Study Completion Date :||July 1, 2023|
Experimental: Treatment (olaparib, high-dose chemotherapy, transplant)
Participants receive olaparib PO BID on days -11 to -3, vorinostat PO on days -10 to -3, gemcitabine IV over 4.5 hours on days -9 and -4, busulfan IV over 3 hours on day -9 to -6, melphalan IV over 30 minutes on days -4 and -3, and undergo peripheral blood stem cell transplant IV over 30-60 minutes on day 0. Patients with CD20+ tumors also receive rituximab IV over 3-6 hours on day -10.
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo peripheral blood stem cell transplant
Other: Pharmacokinetic Study
Rituximab 375 mg/m2 for patients with CD20+ tumors on Day -10 in the AM as an inpatient.
- Dose limiting toxicities (DLT) [ Time Frame: Up to 30 days ]All adverse events will be tabulated by dose, and a Bayesian DLT curve will be fit.
- Overall survival (OS) [ Time Frame: At 2 years ]OS will be estimated by the method of Kaplan and Meier. Participants without an event at the analysis time point (2 years) will be censored.
- Event-free survival (EFS) [ Time Frame: At 2 years ]EFS will be estimated by the method of Kaplan and Meier. Patients without an event at the analysis time point (2 years) will be censored. EFS is the time to relapse, secondary hematological malignancy, death, whichever occurred first, or last follow-up.
- Objective response (OR) [ Time Frame: Up to 100 days ]OR will be tabulated by dose, and a Bayesian DLT curve will be fit.
- Complete response (CR) [ Time Frame: At 100 days ]CR will be tabulated by dose, and a Bayesian DLT curve will be fit.
- Incidence of adverse events [ Time Frame: At 2 years ]All adverse events will be tabulated by dose, and a Bayesian DLT curve will be fit.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03259503
|Contact: Yago Nieto, MD, PHDemail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Yago L. Nieto 713-792-8750|
|Principal Investigator: Yago L. Nieto|
|Principal Investigator:||Yago L Nieto||M.D. Anderson Cancer Center|