NCT03259503

Olaparib and High-Dose Chemotherapy in Treating Patients With Relapsed or Refractory Lymphomas Undergoing Stem Cell Transplant

Olaparib Combined With High-Dose Chemotherapy for Refractory Lymphomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of olaparib when given together with high-dose chemotherapy in treating patients with lymphomas that have come back or does not treatment and are undergoing stem cell transplant. Drugs used in chemotherapy, such as olaparib, vorinostat, gemcitabine, 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. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and high-dose chemotherapy together may work better in treating patients with relapsed/refractory lymphomas undergoing stem cell transplant than with chemotherapy alone.

Detailed description

PRIMARY OBJECTIVE: I. Establish the maximum tolerated dose (MTD) of olaparib combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant \[ASCT\]). SECONDARY OBJECTIVES: 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. Patients 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, patients are followed up every 1-2 days for 30 days and then every 2 weeks for up to 100 days.

Conditions

• 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

Interventions

Type	Name	Description
DRUG	Busulfan	Given IV
DRUG	Gemcitabine	Given IV
DRUG	Melphalan	Given IV
DRUG	Olaparib	Given PO
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo peripheral blood stem cell transplant
OTHER	Pharmacokinetic Study	Correlative studies
BIOLOGICAL	Rituximab	Given IV
DRUG	Vorinostat	Given PO

Timeline

• Start date: 2019-09-13
• Primary completion: 2025-11-05
• Completion: 2025-11-05
• First posted: 2017-08-23
• Last updated: 2025-11-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study