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Diffuse Large B-Cell LymphomaPhase 1/2NCT03147885

Selinexor Plus Combination Chemotherapy in Treating Patients With Advanced B Cell Non-Hodgkin Lymphoma

A Phase 1/2 study testing Selinexor in people with Diffuse Large B-Cell Lymphoma and Recurrent B-Cell Non-Hodgkin Lymphoma, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase Ib/II trial is aimed at studying the combination of a drug named Selinexor (selective inhibitor of nuclear export) in combination with standard therapy for B cell Non-Hodgkin's lymphoma called R-CHOP. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Selinexor
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
20 Jun 2017to 25 Jun 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phase 1 Part: Patients with pathologically confirmed advanced stage B-cell NHL (Ann Arbor stage 3 or 4) for whom R-CHOP is considered appropriate therapy; newly diagnosed DLBCL, newly diagnosed low grade B cell NHL, and previously treated low grade B cell NHL patients in first relapse after a prior treatment with non-anthracycline containing chemotherapy are allowed; double hit and transformed diffuse large B cell lymphoma are allowed
  • Allowed low grade B cell lymphomas will include follicular lymphoma any grade, marginal zone lymphoma including mucosa-associated lymphoid tissue (MALT) lymphoma, indolent mantle cell lymphoma and Waldenstrom's macroglobulinemia
  • Phase 2 Part: Patients with pathologically confirmed newly diagnosed diffuse large B cell lymphoma (Ann Arbor stage 3 or 4); newly diagnosed double hit and transformed diffuse large B cell lymphoma are allowed
  • Patients must have measurable disease, defined as at least one lesion above and below the diaphragm or stage 4 disease that can be accurately measured in at least one dimension; lymph nodes should be considered abnormal if the long axis is > 1.5 cm, regardless of the short axis
  • Allowed prior therapy:
  • Newly diagnosed DLBCL and low grade B cell lymphoma: No prior therapy is allowed except steroids equivalent to maximum of prednisone 20 mg once daily for maximum of seven days prior to registration
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  • Relapsed/refractory low grade B cell lymphoma (only allowed in phase I): A minimum and maximum of one line of prior non-anthracycline containing therapy is allowed; prior localized radiation therapy is not considered a line
  • For patients who have had prior chemotherapy or immunotherapy, at least 2 weeks must have elapsed between last dose and initial dose of RCHOP-selinexor; for patients treated with radio-immunotherapy, at least 12 weeks
  • All races and ethnic groups are eligible for this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%)
  • Life expectancy of greater than 6 months
  • Premenopausal female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients with DLBCL who have received chemotherapy or immunotherapy (except one week of steroids as described above) at any time point in the past for therapy of the DLBCL; patients with low grade B cell lymphomas who have received more than one prior line of chemotherapy or any anthracycline-containing therapy in the past for their low grade B cell lymphoma; localized radiation therapy does not count as a line of therapy
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases are excluded
  • History of severe allergic reactions (as determined by treating physician) attributed to the drugs being used in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (New York Heart Association [NYHA] class >= 3 or left ventricular ejection fraction < 45%), unstable angina pectoris, myocardial infarction within the last 3 months, clinically significant cardiac arrhythmia (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] permissible), or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and lactating women are excluded
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  • Human immunodeficiency virus (HIV)-positive patients regardless of treatment are excluded; patients with evidence of active hepatitis B and hepatitis C infection with positive real time polymerase chain reaction (qPCR) are also excluded but patients with prior exposure to hepatitis B or C with negative qPCR are allowed
  • Patients with severe intolerance to glucocorticoids
  • Major surgery within 2 weeks of first dose of study drug
  • Patients who are unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study treatment
  • Absolute neutrophil count (ANC) < 1500 cells/mm^3
  • Platelet count < 100,000/mm^3
  • Serum bilirubin > 1.5 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome: total bilirubin of > 3 x ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times ULN
  • Estimated creatinine clearance of < 30 mL/min, calculated using the formula of Cockroft and Gault

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

Other trials in United States

About this study

Official title: A Phase 1b/2 Investigator Initiated Study of RCHOP in Combination With Selinexor (KPT-330) in B Cell Non-Hodgkin's Lymphoma

This phase Ib/II trial is aimed at studying the combination of a drug named Selinexor (selective inhibitor of nuclear export) in combination with standard therapy for B cell Non-Hodgkin's lymphoma called R-CHOP. The investigators will establish maximum tolerated dose of Selinexor in combination with RCHOP and also study the efficacy of this combination for therapy of B cell Non-Hodgkin's lymphoma. Giving Selinexor plus chemotherapy may work better in treating patients with B cell non-Hodgkin lymphoma.

Read the detailed description

The study will be done in two phases namely phase 1B and phase 2.

In the phase 1B component the investigators intend to enroll patients in a 3+3 dose escalation design. Newly diagnosed indolent and diffuse large cell lymphomas as well as relapsed/refractory indolent B cell lymphomas are eligible for enrollment in the phase 1 component. The primary end-point for this component would be to establish the recommended phase 2 dose (RP2D) for Selinexor in combination with standard dose RCHOP chemotherapy.

In the phase 2 part of the study the investigators will use recommended phase 2 dose of Selinexor plus standard dose RCHOP combination to treat newly diagnosed DLBCL patients with the primary end-point being 2 year Progression free survival.

Maintenance Phase: Patients with Follicular Lymphoma and Diffuse Large B cell lymphoma able to achieve PR or better at the end of therapy scan will be put on maintenance Selinexor for a total of one year. The dose of Selinexor in the maintenance phase would be similar to the last dose used for that particular patient in the treatment phase 1 or 2.

Being tested
Selinexor
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Lymphoma, Non-Hodgkin

What participants receive

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

  • SelinexorDrug

    Also called CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear

    Given PO

Study groups in NCT03147885
Study groupRoleWhat they receive
Treatment (selinexor, RCHOP)ExperimentalPatients will receive selinexor PO on days 1, 8, and 15 of a 21 week cycle. RCHOP will be given at standard dosing every 21 days. In the phase 1 part there is dose escalation for Selinexor in a 3+3 design. Treatment will be given for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response or better will receive maintenance selinexor PO on days 1, 8, 15, and 22 every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Selinexor

What is being measured

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

  1. Maximum tolerated dose of selinexor in combination with RCHOP chemotherapy defined as =< 1/6 patients experience a dose limiting toxicity (Phase Ib)

    Toxicity grading in both phase 1b and phase 2 parts will be done based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 guidelines. Toxicity data will be collected at least weekly during the course of treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

    Measured: Up to 21 days

  2. Progression-free survival (PFS) for patients with newly diagnosed DLBCL treated with RCHOP-selinexor combination (Phase II)

    PFS will be described with Kaplan-Meier curves and estimated medians with 95% confidence intervals.

    Measured: From baseline to disease progression or death from any cause, assessed up to 2 years

Secondary outcomes (7)

  1. CR of patients with newly DLBCL treated with selinexor and RCHOP

    Response rates will be estimated as proportions with 95% Wilson confidence intervals.

    Measured: Up to 2 years

  2. PR of patients with newly diagnosed DLBCL treated with selinexor and RCHOP

    Response rates will be estimated as proportions with 95% Wilson confidence intervals.

    Measured: Up to 2 years

  3. SD of patients with newly diagnosed DLBCL treated with selinexor and RCHOP

    Response rates will be estimated as proportions with 95% Wilson confidence intervals.

    Measured: Up to 2 years

  4. ORR (CR and PR) of patients with newly diagnosed DLBCL treated with selinexor and RCHOP

    Response rates will be estimated as proportions with 95% Wilson confidence intervals.

    Measured: Up to 2 years

  5. OS of patients with newly diagnosed DLBCL treated with RCHOP-selinexor combination

    OS will be described with Kaplan-Meier curves and estimated medians with 95% confidence intervals.

    Measured: Baseline to date of death, assessed up to 2 years

  6. Change in CRM1/XPO-1 activity expression assessed in tissue by polymerase chain reaction (PCR)

    Difference in the CRM-1 activity by PCR in the tumor tissue and peripheral blood samples obtained at baseline and at 48-72 hours after cycle 1 day1 of therapy.

    Measured: Baseline and at 48-72 hours after cycle 1 day 1

  7. Change in CRM1/XPO-1 activity expression assessed in tissue by immunohistochemistry (IHC)

    Difference in the CRM-1 activity by IHC in the tumor tissue and peripheral blood samples obtained at baseline and at 48-72 hours after cycle 1 day1 of therapy.

    Measured: Baseline and at 48-72 hours after cycle 1 day 1

Timeline

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

  1. First posted10 May 2017
  2. Study start20 Jun 2017
  3. Primary completion25 Jun 2027 (estimated)
  4. Study completion25 Jun 2027 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03147885
Sponsor's protocol ID
2016-125
Other IDs
P30CA022453
Status last verified
Oct 2026
First submitted
5 May 2017
Last updated
23 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Seymour EK, Khan HY, Li Y, Chaker M, Muqbil I, Aboukameel A, Ramchandren R, Houde C, Sterbis G, Yang J, Bhutani D, Pregja S, Reichel K, Huddlestun A, Neveux C, Corona K, Landesman Y, Shah J, Kauffman M, Shacham S, Mohammad RM, Azmi AS, Zonder JA. Selinexor in Combination with R-CHOP for Frontline Treatment of Non-Hodgkin Lymphoma: Results of a Phase I Study. Clin Cancer Res. 2021 Jun 15;27(12):3307-3316. doi: 10.1158/1078-0432.CCR-20-4929. Epub 2021 Mar 30.

    PubMed 33785483

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Selinexor in people with Diffuse Large B-Cell Lymphoma and Recurrent B-Cell Non-Hodgkin Lymphoma, run by Barbara Ann Karmanos Cancer Institute 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 13 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 23 Oct 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Maximum tolerated dose of selinexor in combination with RCHOP chemotherapy defined as =< 1/6 patients experience a dose limiting toxicity (Phase Ib) (time frame: Up to 21 days). The study lists 2 primary outcomes in all. 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 NCT03147885, which also lists 1 linked publication.

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 23 Oct 2026.

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