A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP

NCT02741388 | Completed Phase 1 DMC

• 1 other identifier: SELINDA
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 8

Brief Summary

This is an open label, multicenter, dose escalation, phase Ib study to determine the recommended phase II dose (RP2D), by assessing the maximum tolerated dose (MTD), safety and preliminary efficacy of selinexor in adult patients with relapsed/refractory B-cell malignancies receiving either R-DHAOx (Group A) or R-GDP (Group B). This dose escalation phase will be followed by an exploratory expansion phase in the same population with 12 patients enrolled in each group, who will receive selinexor at the RP2D. The "3+3" design will be applied for dose escalation. The escalation will be performed independently in two distinct groups:

• Group A : Oral selinexor + R-DHAOx for 3 cycles (3-week cycles)
• Group B: Oral selinexor + R-GDP for 3 cycles (3-week cycles) The choice of the conventional immunotherapy regimen which will be administered to each patient, R-DHAOx (Group A) or R-GDP (Group B), is left at the investigator's decision before patient's inclusion. Different dose levels for selinexor administration will be examined sequentially in each group by the Dose Escalation Committee (DEC): 4 doses of selinexor per 3-week cycle at 20 mg flat (Dose Level -1, DL-1), 40 mg flat (DL1), 60 mg flat (DL2) or 80 mg flat (DL3) will be taken orally by the patient on D1, D3, D8 and D10 of each cycle (dosing weeks = week 1 and week 2 of each 3-week cycle). Dose escalation will begin at DL1 and will continue until the MTD is exceeded or until the highest dose level defined in the study (DL3) is reached. Dose escalation to the next planned dose level will be decided by the DEC based on the number of DLTs observed during the DLT assessment period. The dose escalation phase will be followed by an exploratory expansion phase in the same two groups (Groups A and B), depending on the decision of the Independent Data Monitoring Committee (IDMC) after review of safety data at the end of dose escalation part. Patients enrolled in the expansion phase will receive selinexor at the RP2D defined by the IDMC, together with either of the conventional regimen R-DHAOx or R-GDP (left at the investigator's choice).

Conditions

B-cell Lymphoma

Keywords

selinexor; lymphoma; inhibitor of nuclear export

Outcome Measures

Primary Outcomes (1)

• Incidence rate of dose-limiting toxicities (DLTs) observed during the DLT assessment period (cycle 1) at each dose level examined

  Up to 35 days

Secondary Outcomes (6)

• Response rates

  3 months

• Duration of response

  3 years

• Progression-free survival (PFS)

  3 years

• Time to next anti-lymphoma treatment (TTNLT)

  3 years

• Overall survival (OS)

  3 years

Study Arms (1)

Selinexor + immunochemotherapy

EXPERIMENTAL

Selinexor will be administered orally on Day1, 3, 8 and 10 of each 3-week cycle with an immunochemotherapy, R-DHAOx (Group A: rituximab + dexamethasone + oxaliplatin + cytarabine) or R-GDP (Group B: rituximab + dexamethasone + gemcitabine + cisplatin) for 3 cycles (choice of the immunochemotherapy left at the investigator's decision before patient's inclusion). Different dose levels of selinexor will be examined sequentially in each group: 20 mg flat (DL-1), 40 mg flat (DL1), 60 mg flat (DL2), 80 mg flat (DL3).

Drug: selinexor; Drug: Rituximab; Drug: Dexamethasone; Drug: Oxaliplatin; Drug: Cisplatin; Drug: Cytarabine; Drug: Gemcitabine

Interventions

selinexor DRUG

Also known as: KPT-330

Selinexor + immunochemotherapy

Rituximab DRUG

Selinexor + immunochemotherapy

Dexamethasone DRUG

Selinexor + immunochemotherapy

Oxaliplatin DRUG

Selinexor + immunochemotherapy

Cisplatin DRUG

Selinexor + immunochemotherapy

Cytarabine DRUG

Selinexor + immunochemotherapy

Gemcitabine DRUG

Selinexor + immunochemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with any type of relapsed or refractory B-cell lymphoma
• Eligible to receive R-DHAOx or R-GDP regarding the investigator's opinion
• Who received prior therapy with at least one but no more than two lines therapies for B-Cell Lymphoma
• Patient must have measurable disease defined by at least one single node or tumor lesion \> 1.5 cm
• Aged between 18 years and 70 years (included) on date of consent signature
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• With a life expectancy of ≥ 3 months
• Having signed a written informed consent
• Male patients (if sexually active with a woman of childbearing potential) must agree to use a reliable method of birth control during the study treatment and for at least 6 months after the last study drug administration. Male patients must agree to not donate sperm during the study treatment and for at least 6 months after the last study drug administration
• Female patients of childbearing potential must agree to use two reliable methods of birth control during study treatment and for 6 months after the last dose and have a negative serum human chorionic gonadotropin (hCG) pregnancy test within 3 days prior to C1D1. Reliable methods of contraception include intrauterine devices, hormonal contraceptives \[contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release\], abstinence or sterilization of the partner.

You may not qualify if:

• Previous treatment with selinexor
• Known central nervous system or meningeal involvement by lymphoma
• Contraindication to any drug contained in these regimen
• Subjects with known Human Immunodeficiency Virus (HIV) positivity
• Subjects with known active Hepatitis B (HB) infection (positive Ag HBs) or positive serology to hepatitis B (Ag HBs or antibody anti-HB c or positive DNA PCR) or active Hepatitis C (HCV) infection (patients with positive HCV serology are eligible only if PCR is negative for known HCV RNA)
• Subjects with any uncontrolled active systemic infection requiring intravenous (IV) antibiotics
• Any of the following laboratory abnormalities within 14 days prior to first administration (C1D1) of study treatment:
• Absolute neutrophil count (ANC) \< 1,000 cells/mm3 (1.0 x 109/L)
• Spontaneous (within 7 days of any platelet transfusion) platelet count \< 100,000/mm3 (100 x 109/L) (75 x 109/L if due to lymphoma)
• Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \> 5.0 x upper limit of normal (ULN)
• Serum total bilirubin \> 2x Upper Limit of Normal (ULN), or \> 5x ULN if due to Gilbert syndrome or lymphoma involvement
• Creatinine clearance \< 50 mL /min (for patients who will receive DHAOx) or \< 70 mL/min (for GDP)
• Subjects with pre-existing ≥ Grade 2 neuropathy
• Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the subject has been free of the disease for ≥ 3 years
• Any life-threatening illness, serious active disease or co-morbid medical condition, laboratory abnormality, organ system dysfunction or psychiatric illness which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of selinexor, or put the study outcomes at undue risk, or that would prevent the subject from signing the informed consent form

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (8)

Institut Jules Bordet

Brussels, Belgium

Location

CHU Dijon

Dijon, France

Location

CHRU de Lille - Hôpital Claude Huriez

Lille, France

Location

CHU Montpellier - Hôpital Saint Eloi

Montpellier, France

Location

CHU Nancy - Hôpital de Brabois

Nancy, France

Location

Hôpital Saint-Louis

Paris, France

Location

CHU Bordeaux - Centre François Magendie

Pessac, France

Location

Centre Henri Becquerel

Rouen, France

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma

Interventions

selinexor; Rituximab; Dexamethasone; Oxaliplatin; Cisplatin; Cytarabine; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine

Study Officials

• Hervé TILLY, MD

  Centre Henri Becquerel, Rouen, France - LYSA

  STUDY CHAIR

• Marie MAEREVOET, MD

  Institut Jules Bordet, Bruxelles, Belgium - LYSA

  STUDY CHAIR

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: April 14, 2016
• First Posted: April 18, 2016
• Study Start: October 1, 2016
• Primary Completion: September 29, 2021
• Study Completion: September 29, 2021
• Last Updated: December 7, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); FR (7)