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

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by The Lymphoma Academic Research Organisation
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT02741388
First received: April 14, 2016
Last updated: March 8, 2017
Last verified: March 2017
  Purpose

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).


Condition Intervention Phase
B-cell Lymphoma Drug: selinexor Drug: Rituximab Drug: Dexamethasone Drug: Oxaliplatin Drug: Cisplatin Drug: Cytarabine Drug: Gemcitabine Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP

Resource links provided by NLM:


Further study details as provided by The Lymphoma Academic Research Organisation:

Primary Outcome Measures:
  • Incidence rate of dose-limiting toxicities (DLTs) observed during the DLT assessment period (cycle 1) at each dose level examined [ Time Frame: Up to 35 days ]

Secondary Outcome Measures:
  • Response rates [ Time Frame: 3 months ]
    Response rates will be evaluated according to the Lugano 2014 response criteria based on disease response assessment on Positron emission tomography-computed tomography (PET-CT) performed after completion of the 3 cycles of treatment (for patients who received all 3 cycles) or at permanent discontinuation of treatment (PTD evaluation, within 4 weeks after the last drug administration).

  • Duration of response [ Time Frame: 3 years ]
    Duration of response is defined as the time of attainment of complete response (CR) or partial response (PR) to the date of first documented disease progression, relapse or death from any cause.

  • Progression-free survival (PFS) [ Time Frame: 3 years ]
    PFS is defined as the time from inclusion into the study to the first observation of documented disease progression or death due to any cause.

  • Time to next anti-lymphoma treatment (TTNLT) [ Time Frame: 3 years ]
    TTNLT is defined as the time from the date of inclusion to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radio-immunotherapy or immunotherapy, with the exception of High Dose Therapy/ASCT).

  • Overall survival (OS) [ Time Frame: 3 years ]
    Overall survival is defined as the time from the date of inclusion to the date of death from any cause.

  • Incidence of grade ≥ 2 renal toxicities, grade ≥ 2 neuropathy, and grade ≥ 3 toxicities [ Time Frame: 3 months ]

Estimated Enrollment: 60
Actual Study Start Date: October 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Selinexor + immunochemotherapy

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
Other Name: KPT-330
Drug: Rituximab Drug: Dexamethasone Drug: Oxaliplatin Drug: Cisplatin Drug: Cytarabine Drug: Gemcitabine

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with any type of relapsed or refractory B-cell lymphoma
  2. Eligible to receive R-DHAOx or R-GDP regarding the investigator's opinion
  3. Who received prior therapy with at least one but no more than two lines therapies for B-Cell Lymphoma
  4. Patient must have measurable disease defined by at least one single node or tumor lesion > 1.5 cm
  5. Aged between 18 years and 70 years (included) on date of consent signature
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  7. With a life expectancy of ≥ 3 months
  8. Having signed a written informed consent
  9. 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
  10. 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.

Exclusion Criteria:

  1. Previous treatment with selinexor
  2. Known central nervous system or meningeal involvement by lymphoma
  3. Contraindication to any drug contained in these regimen
  4. Subjects with known Human Immunodeficiency Virus (HIV) positivity
  5. 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)
  6. Subjects with any uncontrolled active systemic infection requiring intravenous (IV) antibiotics
  7. Any of the following laboratory abnormalities within 14 days prior to first administration (C1D1) of study treatment:

    1. Absolute neutrophil count (ANC) < 1,000 cells/mm3 (1.0 x 109/L)
    2. 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)
    3. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5.0 x upper limit of normal (ULN)
    4. Serum total bilirubin > 2x Upper Limit of Normal (ULN), or > 5x ULN if due to Gilbert syndrome or lymphoma involvement
  8. Creatinine clearance < 50 mL /min (for patients who will receive DHAOx) or < 70 mL/min (for GDP)
  9. Subjects with pre-existing ≥ Grade 2 neuropathy
  10. 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
  11. 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
  12. Pregnant or breastfeeding women
  13. Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy (administration of glucocorticoids should not exceed 1mg/kg/day in the 14 days prior to C1D1)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02741388

Contacts
Contact: Chloé Gourc Berthod +334 72 66 93 33

Locations
Belgium
Institut Jules Bordet Recruiting
Bruxelles, Belgium
Contact: Marie MAEREVOET, MD    +32 25 41 32 12      
Principal Investigator: Marie MAEREVOET, MD         
France
CHU Dijon Recruiting
Dijon, France
Contact: Olivier CASASNOVAS, MD    +33380295041      
Principal Investigator: Olivier CASASNOVAS, MD         
CHRU de Lille - Hôpital Claude Huriez Recruiting
Lille, France
Contact: Franck MORSCHHAUSER, MD    +33320445713      
Principal Investigator: Franck MORSCHHAUSER, MD         
CHU Montpellier - Hôpital Saint Eloi Recruiting
Montpellier, France
Contact: Guillaume CARTRON, MD    +33467338079      
Principal Investigator: Guillaume CARTRON, MD         
CHU Nancy - Hôpital de Brabois Recruiting
Nancy, France
Contact: Pierre FEUGIER, MD    +33383153282      
Principal Investigator: Pierre FEUGIER, MD         
Hôpital Saint-Louis Recruiting
Paris, France
Contact: Catherine THIEBLEMONT, MD    +33142499236      
Principal Investigator: Catherine THIEBLEMONT, MD         
CHU Bordeaux - Centre François Magendie Recruiting
Pessac, France
Contact: Kamal BOUABDALLAH    +33557656511      
Principal Investigator: Kamal BOUABDALLAH, MD         
Centre Henri Becquerel Recruiting
Rouen, France
Contact: Hervé TILLY, MD    +33232082202      
Principal Investigator: Hervé TILLY, MD         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Karyopharm Therapeutics Inc
Investigators
Study Chair: Hervé TILLY, MD Centre Henri Becquerel, Rouen, France - LYSA
Study Chair: Marie MAEREVOET, MD Institut Jules Bordet, Bruxelles, Belgium - LYSA
  More Information

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT02741388     History of Changes
Other Study ID Numbers: SELINDA
Study First Received: April 14, 2016
Last Updated: March 8, 2017

Keywords provided by The Lymphoma Academic Research Organisation:
selinexor
lymphoma
inhibitor of nuclear export

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Oxaliplatin
Cisplatin
Dexamethasone
Rituximab
Cytarabine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antiemetics

ClinicalTrials.gov processed this record on June 28, 2017