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B-cell LymphomaPhase 1SELINDANCT02741388

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

A Phase 1 study testing selinexor, Rituximab and Dexamethasone in people with B-cell Lymphoma, run by The Lymphoma Academic Research Organisation at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
B-cell Lymphoma
What is being tested?
selinexor, Rituximab and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
8 sitesin 2 countries
Study dates
Oct 2016to 29 Sep 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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
  • Pregnant or breastfeeding women
  • 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)

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

France7 sites

  • CHU Dijon

    Dijon

  • CHRU de Lille - Hôpital Claude Huriez

    Lille

  • CHU Montpellier - Hôpital Saint Eloi

    Montpellier

  • CHU Nancy - Hôpital de Brabois

    Nancy

  • Hôpital Saint-Louis

    Paris

  • CHU Bordeaux - Centre François Magendie

    Pessac

  • Centre Henri Becquerel

    Rouen

Other trials in France

Belgium1 site

  • Institut Jules Bordet

    Brussels

Other trials in Belgium

About this study

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:

Read more
  • 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
Being tested
selinexor, Rituximab, Dexamethasone, Oxaliplatin, Cisplatin
Keywords
selinexor, lymphoma, inhibitor of nuclear export
Medical subject headings
Lymphoma, B-Cell, Lymphoma

What participants receive

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

Study groups in NCT02741388
Study groupRoleWhat they receive
Selinexor + immunochemotherapyExperimentalSelinexor 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).
Receives: Drug: selinexor; Drug: Rituximab; Drug: Dexamethasone; Drug: Oxaliplatin; Drug: Cisplatin; Drug: Cytarabine; Drug: Gemcitabine

What is being measured

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

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

    Measured: Up to 35 days

Secondary outcomes (6)

  1. Response rates

    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).

    Measured: 3 months

  2. Duration of response

    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.

    Measured: 3 years

  3. Progression-free survival (PFS)

    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.

    Measured: 3 years

  4. Time to next anti-lymphoma treatment (TTNLT)

    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).

    Measured: 3 years

  5. Overall survival (OS)

    Overall survival is defined as the time from the date of inclusion to the date of death from any cause.

    Measured: 3 years

  6. Incidence of grade ≥ 2 renal toxicities, grade ≥ 2 neuropathy, and grade ≥ 3 toxicities

    Measured: 3 months

Timeline

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

  1. First posted18 Apr 2016 (estimated)
  2. Study startOct 2016
  3. Primary completion29 Sep 2021
  4. Study completion29 Sep 2021

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02741388
Sponsor's protocol ID
SELINDA
Acronym
SELINDA
Status last verified
Dec 2021
First submitted
14 Apr 2016
Last updated
7 Dec 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing selinexor, Rituximab and Dexamethasone in people with B-cell Lymphoma, run by The Lymphoma Academic Research Organisation at 8 sites in 2 countries.

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 10 inclusion and 17 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: finished, as of the sponsor's last update on 7 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in France, Belgium. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

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). 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 NCT02741388.

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 7 Dec 2021.

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