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Recurrent Diffuse Large B-Cell LymphomaPhase 1NCT03259503

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

A Phase 1 study testing Busulfan, Gemcitabine and Melphalan in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent T-Cell Non-Hodgkin Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Busulfan, Gemcitabine and Melphalan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
13 Sep 2019to 5 Nov 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18-65
  • Patients with:
  • 2.1 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.
  • 2.2 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.
  • 2.2.3 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.]
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  • 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:
  • 11.1 Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.
  • 11.2 Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50.
  • 11.3 Radiation-induced oophorectomy with last menses >1 year ago. 11.4 Chemotherapy-induced menopause with >1 year interval since last menses. 11.5 Surgical sterilization (bilateral oophorectomy or hysterectomy). 11.6 Female patients must agree to use a highly effective birth control method while on study and for at least 6 months after the last dose of study drug(s).
  • Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after last dose of study drug(s) to prevent pregnancy in a partner.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • Prior apheresis of >/= 3 million CD34+ cells/Kg.
  • Eligibility for ASCT is determined by the above inclusion criteria 3-7.

Who cannot join

  • 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).
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  • 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.
  • Uncontrolled non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Breast feeding women.
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
  • Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Olaparib Combined With High-Dose Chemotherapy for Refractory Lymphomas

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Establish the maximum tolerated dose (MTD) of olaparib combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant [ASCT]).

SECONDARY OBJECTIVES:

  1. 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.

Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, T-Cell, Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU-0059436

    Given PO

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support

    Undergo peripheral blood stem cell transplant

  • Pharmacokinetic StudyOther

    Also called PHARMACOKINETIC, PK Study

    Correlative studies

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT03259503
Study groupRoleWhat they receive
Treatment (olaparib, high-dose chemotherapy, transplant)ExperimentalPatients 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.
Receives: Drug: Busulfan; Drug: Gemcitabine; Drug: Melphalan; Drug: Olaparib; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacokinetic Study; Biological: Rituximab; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicities (DLT)

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

    Measured: Up to 30 days

Secondary outcomes (5)

  1. Overall survival (OS)

    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.

    Measured: At 2 years

  2. Event-free survival (EFS)

    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.

    Measured: At 2 years

  3. Objective response (OR)

    OR will be tabulated by dose, and a Bayesian DLT curve will be fit.

    Measured: Up to 100 days

  4. Complete response (CR)

    CR will be tabulated by dose, and a Bayesian DLT curve will be fit.

    Measured: At 100 days

  5. Incidence of adverse events

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

    Measured: At 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2017
  2. Study start13 Sep 2019
  3. Primary completion5 Nov 2025
  4. Study completion5 Nov 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03259503
Sponsor's protocol ID
2017-0073
Other IDs
NCI-2018-01094, 2017-0073
Status last verified
Nov 2025
First submitted
22 Aug 2017
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Busulfan, Gemcitabine and Melphalan in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent T-Cell Non-Hodgkin Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (DLT) (time frame: Up to 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03259503.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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