Prolymphocytic LeukemiaPhase 1NCT02303392
Selinexor and Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Aggressive Non-Hodgkin Lymphoma
A Phase 1 study testing Selinexor, Ibrutinib and Pharmacological Study in people with Prolymphocytic Leukemia and Recurrent Adult Diffuse Large Cell Lymphoma, run by Jennifer Woyach at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prolymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma
- What is being tested?
- Selinexor, Ibrutinib and Pharmacological Study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Jun 2015to 18 Apr 2022
- Phase
- Phase 1
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
- 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
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- 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
Who cannot join
- 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
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- 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
- Patients must have recovered all toxicities from prior therapy or radiation to grade 1 or less (excluding alopecia)
- Patients may not have had major surgery within 10 days of enrollment, or minor surgery within 7 days of enrollment; examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint; the decision about whether a surgery is major or minor can be made at the discretion of the treating physician
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with markedly decreased visual acuity
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Dose Escalation Study of Selinexor (KPT-330), a Selective Inhibitor of Nuclear Export, and Ibrutinib, a Bruton's Tyrosine Kinase Inhibitor, in Patients With Relapsed and Refractory Chronic Lymphocytic Leukemia or Aggressive Non-Hodgkin Lymphoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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).
SECONDARY OBJECTIVES:
- To characterize the safety and tolerability of the combination of selinexor and ibrutinib in patients with relapsed or refractory CLL/SLL/PLL or aggressive NHL.
II. To characterize the pharmacokinetic (PK) properties of the combination of selinexor and ibrutinib in patients with relapsed or refractory CLL/SLL/PLL or aggressive NHL.
III. To obtain preliminary evidence on efficacy of the combination of selinexor and ibrutinib in patients with relapsed or refractory CLL/SLL/PLL or aggressive NHL.
IV. To obtain preliminary evidence of response in CLL/SLL/PLL and diffuse large B-cell lymphoma (DLBCL) patients receiving the combination of selinexor and ibrutinib as related to CLL/SLL/PLL karyotype and immunoglobulin variable heavy chain (IgVH) mutational status and DLBCL subtype, respectively.
- To evaluate the inhibition of the B-cell receptor signaling pathway in patients with relapsed or refractory CLL/SLL/PLL who receive the combination of selinexor and ibrutinib.
VI. To evaluate the change in localization of tumor suppressor and growth regulation proteins in patients with relapsed or refractory CLL/SLL/PLL following treatment with selinexor in general and as related to response.
VII. To preliminarily assess potential causes for primary and secondary resistance to selinexor and ibrutinib.
VIII. To measure intracellular levels of selinexor and metabolites in peripheral blood mononuclear cells and to identify how this relates to pharmacodynamics effects and clinical outcomes.
OUTLINE: This is a dose-escalation study of selinexor.
Patients receive ibrutinib orally (PO) on days 8-28 of course 1 and on days 1-28 on subsequent courses and selinexor PO twice daily (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.
After completion of study treatment, patients are followed up at 4 weeks and then every 6 months thereafter.
- Conditions
- Prolymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia
- Being tested
- Selinexor, Ibrutinib, Pharmacological Study, Laboratory Biomarker Analysis
- Medical subject headings
- Leukemia, Prolymphocytic, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell
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 Export KPT-330, SINE KPT-330
Given PO
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given PO
Also called pharmacological studies
Correlative studies
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Selinexor; Drug: Ibrutinib; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Day 28
Secondary outcomes (4)
Number of Participants With Toxicities Graded by CTCAE V4 That Are Grade 3 or Higher
Toxicities will be tabulated by type and grade and displayed in summary form. In addition, the number of courses started/completed, number of patients requiring dose reductions, and the reason for going off treatment may be summarized to assess treatment tolerability.
Measured: Up to 4 years
Clinical Response Defined as Those With CR or PR
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 4 years
Progression Free Survival (PFS)
Progression Free Survival (PFS): PFS calculated from the date of study enrollment to disease progression or death, whichever occurs first. Patients who do not progress or die will be censored at the time of last contact with response assessment by physical exam and laboratory studies.
Measured: Date of study enrollment to disease progression or death, whichever occurs first assessed up to 4 years
Overall Survival (OS)
Overall Survival (OS) calculated from the date of study enrollment to death. Patients who do not die will be censored at the time of last contact. This will be analyzed in each cohort independently
Measured: Date of study enrollment to death assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2014 (estimated)
- Study start9 Jun 2015
- Primary completion18 Apr 2022
- Study completion18 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prolymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jennifer Woyach
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Responsible party
- Sponsor-investigator, Jennifer Woyach, Ohio State University Comprehensive Cancer Center
- Investigators
- Jennifer Woyach, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02303392
- Sponsor's protocol ID
- OSU-14087
- Other IDs
- NCI-2014-01493
- Status last verified
- May 2025
- First submitted
- 25 Nov 2014
- Last updated
- 10 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35608822