Selinexor and Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Aggressive Non-Hodgkin Lymphoma

NCT02303392 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: OSU-14087NCI-2014-01493
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of selinexor when given together with ibrutinib in treating patients with chronic lymphocytic leukemia or aggressive non-Hodgkin lymphoma that has returned after a period of improvement or does not respond to treatment. Drugs used in chemotherapy, such as selinexor, 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. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving selinexor together with ibrutinib may be a better treatment for chronic lymphocytic leukemia or aggressive non-Hodgkin lymphoma.

Conditions

Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose for Selinexor

  To determine the maximum tolerated dose for the combination of selinexor and ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia(SLL)/B-cell prolymphocytic leukemia (PLL) or aggressive non-Hodgkin lymphoma (NHL).

  Day 28

• Maximum Tolerated Dose for Ibrutinib

  To determine the maximum tolerated dose for the combination of selinexor and ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia(SLL)/B-cell prolymphocytic leukemia (PLL) or aggressive non-Hodgkin lymphoma (NHL).

  Day 28

Secondary Outcomes (4)

• Number of Participants With Toxicities Graded by CTCAE V4 That Are Grade 3 or Higher

  Up to 4 years

• Clinical Response Defined as Those With CR or PR

  Up to 4 years

• Progression Free Survival (PFS)

  Date of study enrollment to disease progression or death, whichever occurs first assessed up to 4 years

• Overall Survival (OS)

  Date of study enrollment to death assessed up to 5 years

Study Arms (1)

Treatment (selinexor, ibrutinib)

EXPERIMENTAL

Patients receive ibrutinib PO on days 8-28 of course 1 and on days 1-28 on subsequent courses and selinexor PO BID weekly on day 1 or bi-weekly on days 1 and 3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Selinexor; Drug: Ibrutinib; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

Interventions

Selinexor DRUG

Given PO

Also known as: CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330

Treatment (selinexor, ibrutinib)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (selinexor, ibrutinib)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (selinexor, ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (selinexor, ibrutinib)

Eligibility Criteria

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

You may qualify if:

• A histologically confirmed diagnosis of CLL according the International Workshop on CLL/SLL/B-cell PLL or variant of these (IWCLL or World Health Organization \[WHO\] Criteria) and meet criteria for treatment or have need for cytoreduction for stem cell transplantation or alternative cell therapy; OR
• A histologically confirmed diagnosis of mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL) de novo or in the setting of transformation from an indolent lymphoma (including DLBCL not otherwise specified) according to the World Health Organization criteria for diagnosis of NHL; AND
• Patients must have received at least one prior therapy for CLL or NHL, need additional treatment, and meet criteria for relapsed or refractory disease; they may not be a candidate for curative therapy; relapsed disease is defined as a patient who previously achieved a complete remission (CR) or a partial remission (PR), but after a period of six or more months demonstrates evidence of disease progression; refractory disease is defined as progression within six months of the last anti-leukemic or anti-lymphoma therapy, or any response less than a CR or PR
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Patients with NHL must have objective, documented evidence of disease prior to study entry
• Platelet count \>= 50,000/mm\^3 in the absence of bone marrow involvement; patients with bone marrow involvement only require a platelet count of 30,000/mm\^3
• Absolute neutrophil count \>= 1000/mm\^3 in the absence of bone marrow involvement
• Creatinine clearance (as calculated by Cockroft Gault equation = \[140-age\] \* mass \[kg\]/\[72 \* creatinine mg/dL) \>= 30mL/min
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 2.5 times upper limit of normal (ULN)
• Total bilirubin =\< 2.0 x ULN
• Female patients capable of reproduction and male patients who have partners capable of reproduction must agree to use an effective contraceptive method during the course of the study and for 2 months following the completion of their last treatment
• Female of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test result within 3 days of first study dose; female patients who are surgically sterilized or who are \> 45 years old and have not experienced menses for \> 2 years may have beta-HCG pregnancy test waived
• Patients who are hepatitis B polymerase chain reaction (PCR) negative who have a recent (\< 6 month) history of intravenous immunoglobulin (IVIG) therapy are eligible; patients with a history of hepatitis B (surface antigen or core antibody positive and PCR positive) must take lamivudine or equivalent drug during study therapy and for one year after completion of all therapy; patients on IVIG who are core antibody positive but PCR negative are not mandated to take prophylaxis
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who are concurrently receiving any other investigational agents
• Patients who have received:
• Radiation or chemotherapy =\< 4 weeks
• Mitomycin C, nitrosureas, or radio-immunotherapy =\< 6 weeks, or
• Immunotherapy or targeted therapy (such as kinase inhibitors) =\< 2 weeks prior to cycle 1 day 1(except patients already on ibrutinib)
• Palliative steroids for disease related symptoms are allowed as long as dose is tapered down to an equivalent of =\< 10 mg of oral prednisone daily on cycle 1 day 1
• Patients who have underwent autologous or allogeneic stem cell transplant =\< 4 weeks prior to cycle 1 day 1 or have active graft-versus-host disease are excluded
• Patients unable to swallow capsules, those with uncontrolled vomiting or diarrhea or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as: malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine
• Patients who are 20% below their ideal body weight
• Patients must not be receiving systemic anticoagulation with warfarin; patients must be off warfarin for 30 days prior to enrollment; patients who require anticoagulation with an agent other than warfarin will not be excluded, but must be reviewed by the principal investigator prior to enrollment
• As ibrutinib is extensively metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), and patients must not require continued therapy with a strong inhibitor or inducer of CYP3A4/5
• Patients with active human immunodeficiency virus (HIV) or hepatitis B or C
• Patients with secondary malignancy that requires active systemic therapy that will interfere with interpretation of efficacy or toxicity of selinexor; (Note: patients with basal or squamous skin carcinoma, cervical carcinoma in situ, localized breast cancer requiring hormonal therapy or localized prostate cancer (Gleason score \< 5 are allowed)
• Patients with active known central nervous system (CNS) involvement of CLL or lymphoma; (patients with history of CNS CLL or lymphoma now in remission are eligible for the trial)
• Patients who are pregnant or breast feeding; breastfeeding should be discontinued if the mother is treated with selinexor

Sponsors & Collaborators

• Jennifer Woyach: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (2)

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Stephens DM, Huang Y, Ruppert AS, Walker JS, Canfield D, Cempre CB, Fu Q, Baker S, Hu B, Shah H, Vadeboncoeur R, Rogers KA, Bhat S, Jaglowski SM, Lockman H, Lapalombella R, Byrd JC, Woyach JA. Selinexor Combined with Ibrutinib Demonstrates Tolerability and Safety in Advanced B-Cell Malignancies: A Phase I Study. Clin Cancer Res. 2022 Aug 2;28(15):3242-3247. doi: 10.1158/1078-0432.CCR-21-3867.

  PMID: 35608822 BACKGROUND

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Prolymphocytic; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

selinexor; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Jennifer Woyach
• Organization: The Ohio State University Comprehensive Cancer Center

Jennifer.Woyach@osumc.edu

614-293-8165

Study Officials

• Jennifer Woyach, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: November 27, 2014
• Study Start: June 9, 2015
• Primary Completion: April 18, 2022
• Study Completion: April 18, 2022
• Last Updated: June 10, 2025
• Results First Posted: June 10, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)