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

NCT03259503 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2017-0073NCI-2018-01094
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities (DLT)

  All adverse events will be tabulated by dose, and a Bayesian DLT curve will be fit.

  Up to 30 days

Secondary Outcomes (5)

• Overall survival (OS)

  At 2 years

• Event-free survival (EFS)

  At 2 years

• Objective response (OR)

  Up to 100 days

• Complete response (CR)

  At 100 days

• Incidence of adverse events

  At 2 years

Study Arms (1)

Treatment (olaparib, high-dose chemotherapy, transplant)

EXPERIMENTAL

Patients 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.

Drug: Busulfan; Drug: Gemcitabine; Drug: Melphalan; Drug: Olaparib; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacokinetic Study; Biological: Rituximab; Drug: Vorinostat

Interventions

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (olaparib, high-dose chemotherapy, transplant)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (olaparib, high-dose chemotherapy, transplant)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (olaparib, high-dose chemotherapy, transplant)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Treatment (olaparib, high-dose chemotherapy, transplant)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo peripheral blood stem cell transplant

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (olaparib, high-dose chemotherapy, transplant)

Pharmacokinetic Study OTHER

Correlative studies

Also known as: PHARMACOKINETIC, PK Study

Treatment (olaparib, high-dose chemotherapy, transplant)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (olaparib, high-dose chemotherapy, transplant)

Vorinostat DRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Treatment (olaparib, high-dose chemotherapy, transplant)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65
• Patients with:
• Diffuse large B-cell lymphoma (DLBCL) with one of the following: 2.1.1 Primary refractory (no CR to 1st line) 2.1.2 High-risk relapse, defined as any of the following: CR1 \<6 mo, secondary IPI \>1, or LDH \> 225 U/L. 2.1.3 Refractory relapse: No response to \>/= 1 salvage line and not eligible to receive other novel salvage therapies, such as CAR-T in a timely fashion or have already failed these.
• Hodgkin's with one of the following: 2.2.1 Primary refractory (no CR or PD within 3 months) 2.2.2 High-risk relapse, defined as any of the following: CR1 \<1 year, extranodal relapse, or B symptoms.
• Refractory relapse: No response to \>/= 1 salvage line 2.3 T-non Hodgkin's lymphoma (T-NHL) with one of the following: 2.3.1 Primary refractory (no CR to 1st line) 2.3.2 High-risk relapse (within 6 months) 2.3.3 Refractory relapse to \>/= 1 line of salvage 2.3.4 Any other lymphoma that is refractory or relapsed and that does not qualify for autologous transplant protocols of higher priority.
• Adequate renal function (creatinine clearance estimated using the Cockcroft-Gault equation of \>/= 51 mL/min: Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (xF)a / serum creatinine (mg/dL) x 72 \[a where F=0.85 for females and F=1 for males.\]
• Adequate hepatic function (Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) \</= 3.5 x institutional upper limit of normal unless liver metastases or a systemic inflammatory picture secondary to the lymphoma are present in which case they must be \</= 6x ULN; total bilirubin \</= 2.5 x ULN or \</= 3.5 x ULN if Gilbert's disease)
• Prothrombin time (PT) \</=1.5 x institutional upper limit of normal
• Adequate pulmonary function (FEV1, FVC and DLCOc \>/= 50% of predicted)
• Adequate cardiac function (LVEF \>/= 40%, no uncontrolled arrhythmias or symptomatic cardiac disease
• ECOG performance status \<2
• Provision of informed consent prior to any study specific procedures
• Patients must have a life expectancy \>/= 16 weeks
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days and within 72 hours of study treatment and confirmed prior to receiving treatment on this study. Patients with positive results will be removed from the study. Postmenopausal is defined as one of the following:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.

You may not qualify if:

• Persistent toxicities (\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Prior whole brain irradiation
• Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/= 10,000 copies/mL, or \>/= 2,000 IU/mL)
• Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
• Active infection requiring parenteral antibiotics
• Patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Pregnancy
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumors.
• Resting ECG with QTcF \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Hodgkin Disease

Interventions

Busulfan; Gemcitabine; Melphalan; olaparib; Peripheral Blood Stem Cell Transplantation; Pharmacogenomic Variants; Rituximab; CT-P10; Vorinostat

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Polymorphism, Genetic; Genetic Variation; Genetic Phenomena; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Yago L Nieto

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 23, 2017
• Study Start: September 13, 2019
• Primary Completion: November 5, 2025
• Study Completion: November 5, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)