We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04442022




Registration number
NCT04442022
Ethics application status
Date submitted
10/06/2020
Date registered
22/06/2020
Date last updated
8/03/2021

Titles & IDs
Public title
A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Scientific title
A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)
Secondary ID [1] 0 0
2020-000605-84
Secondary ID [2] 0 0
XPORT-DLBCL-030
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Diffuse Large B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Selinexor (combination therapy)
Treatment: Drugs - Selinexor (combination therapy)
Treatment: Drugs - Selinexor (combination therapy)
Treatment: Drugs - Placebo matching for Selinexor (combination therapy)
Treatment: Drugs - Rituximab (combination therapy)
Treatment: Drugs - Rituximab (combination therapy)
Treatment: Drugs - Gemcitabine (combination therapy)
Treatment: Drugs - Dexamethasone (combination therapy)
Treatment: Drugs - Cisplatin (combination therapy)
Treatment: Drugs - Selinexor (continuous therapy)
Treatment: Drugs - Placebo matching for Selinexor (continuous therapy)

Experimental: Phase 2: Selinexor 40 mg + R-GDP - Patients with RR DLBCL will receive combination therapy of selinexor 40 mg orally at Day 1, and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally once weekly (QW) for each 28-day cycle until progressive disease (PD) or unacceptable toxicity.

Experimental: Phase 2: Selinexor 60 mg + R-GDP - Patients with RR DLBCL will receive combination therapy of selinexor 60 mg orally at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.

Active Comparator: Phase 2: R-GDP - Patients with RR DLBCL will receive R-GDP on specified days (Days 1, 2, 3, 4, and 8) for each 21-day cycle for up to 6 cycles.

Experimental: Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg - Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.

Experimental: Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo - Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.

Placebo Comparator: Phase 3: Placebo + R-GDP followed by Placebo - Patients with RR DLBCL will receive combination therapy of placebo matching for selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.


Treatment: Drugs: Selinexor (combination therapy)
Dose: 40 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral

Treatment: Drugs: Selinexor (combination therapy)
Dose: 60 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral

Treatment: Drugs: Selinexor (combination therapy)
Dose: Selected dose of selinexor (from Phase 2) on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral

Treatment: Drugs: Placebo matching for Selinexor (combination therapy)
Dose: Placebo matching for selected dose of selinexor (from Phase 2) on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral

Treatment: Drugs: Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)

Treatment: Drugs: Rituximab (combination therapy)
Dose: 375 mg/m^2 on Day 1; Route of administration: IV

Treatment: Drugs: Gemcitabine (combination therapy)
Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV

Treatment: Drugs: Dexamethasone (combination therapy)
Dose: 40 mg (20 mg if patient is more than 70 years old) on Days 1, 2, 3, and 4; Route of administration: oral or IV

Treatment: Drugs: Cisplatin (combination therapy)
Dose: 75 mg/m^2 on Day 1; Route of administration: IV

Treatment: Drugs: Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral

Treatment: Drugs: Placebo matching for Selinexor (continuous therapy)
Dose: Placebo matching for 60 mg selinexor QW for each 28-day cycle until PD; Route of administration: oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014
Timepoint [1] 0 0
From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
Primary outcome [2] 0 0
Phase 3: Progression-free Survival (PFS): Based on Lugano Criteria 2014
Timepoint [2] 0 0
From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Secondary outcome [1] 0 0
Phase 2: Progression-free Survival (PFS): Based on Lugano Criteria 2014
Timepoint [1] 0 0
From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Secondary outcome [2] 0 0
Phase 2: Overall Survival (OS)
Timepoint [2] 0 0
From date of initial randomization until death (maximum of 5 years from randomization)
Secondary outcome [3] 0 0
Phase 3: Overall Response Rate (ORR): Based on Lugano Criteria 2014
Timepoint [3] 0 0
From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
Secondary outcome [4] 0 0
Phase 3: Overall Survival (OS)
Timepoint [4] 0 0
From date of initial randomization until death (maximum of 5 years from randomization)
Secondary outcome [5] 0 0
Phase 2: Overall Response Rate at the End of Combination Therapy (ORR-EoC): Based on Lugano Criteria 2014
Timepoint [5] 0 0
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Secondary outcome [6] 0 0
Phase 2: Overall Response Rate at the End of Combination Therapy (ORR-EoC): Based on Modified Lugano Criteria
Timepoint [6] 0 0
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Secondary outcome [7] 0 0
Phase 2: Duration of Response (DOR): Based on Lugano Criteria 2014
Timepoint [7] 0 0
From time of first response until disease progression or death (maximum of 5 years from randomization)
Secondary outcome [8] 0 0
Phase 2: Progression-free Survival (PFS): Based on Modified Lugano Criteria
Timepoint [8] 0 0
From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Secondary outcome [9] 0 0
Phase 2: Number of Patients with Adverse Events (AEs)
Timepoint [9] 0 0
Up to 30 days after last dose of study drug (maximum of 5 years from randomization)
Secondary outcome [10] 0 0
Phase 3: Overall Response Rate at the End of Combination Therapy (ORR-EoC): Based on Lugano Criteria 2014
Timepoint [10] 0 0
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Secondary outcome [11] 0 0
Phase 3: Overall Response Rate at the End of Combination Therapy (ORR-EoC): Based on Modified Lugano Criteria
Timepoint [11] 0 0
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Secondary outcome [12] 0 0
Phase 3: Duration of Response (DOR): Based on Lugano Criteria 2014
Timepoint [12] 0 0
From time of first response until disease progression or death (maximum of 5 years from randomization)
Secondary outcome [13] 0 0
Phase 3: Progression-free Survival (PFS): Based on Modified Lugano Criteria
Timepoint [13] 0 0
From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Secondary outcome [14] 0 0
Phase 3: Number of Patients with Adverse Events (AEs)
Timepoint [14] 0 0
Up to 30 days after last dose of study drug (maximum of 5 years from randomization)

Eligibility
Key inclusion criteria
- Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously
diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade
lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2).
(Documentation to be provided).

- Have received at least 1 but no more than 2 prior lines of systemic therapy for the
treatment of DLBCL (Documentation to be provided).

- Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as
1 line of systemic therapy.

- Maintenance therapy will not be counted as a separate line of systemic therapy.

- Radiation with curative intent for localized DLBCL will not be counted as 1 line of
systemic therapy.

- Positron emission tomography (PET) positive measurable disease with at least 1 node
having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal
lesion with LDi >1 cm (per the Lugano Criteria 2014) (Documentation to be provided).

- Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria
determined by the treating physician. Patients who cannot receive HSCT due to active
disease are allowed on study (up to 10 percent [%] of patients enrolled in each
Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy
must be provided by the treating physician.

- Adequate bone marrow function at screening, defined as (Documentation to be provided):

- Absolute neutrophil count (ANC) =1*10^9 per liter (/L).

- Platelet count =100*10^9/L (without platelet transfusion less than [<] 14 days prior
to Cycle 1 Day 1 [C1D1]).

- Hemoglobin =8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days
prior to C1D1).

- Circulating lymphocytes less than or equal to (=) 50*10^9/L.

- Adequate liver and kidney function, defined as (Documentation to be provided):

- Aspartate transaminase (AST) or alanine transaminase (ALT) =2.5*upper limit of normal
(ULN), or =5*ULN in cases with known lymphoma involvement in the liver.

- Serum total bilirubin =2*ULN, or =5*ULN if due to Gilbert syndrome or in cases with
known lymphoma involvement in the liver.

- Calculated creatinine clearance (CrCl) =30 milliliter per minute (mL/min) based on
Cockcroft-Gault formula.

- Eastern Cooperative Oncology Group (ECOG) performance status of =2.

- An estimated life expectancy of >3 months at Screening.

- Patients with primary refractory DLBCL, defined as no response or relapse within 6
months after ending first-line treatment, will be allowed in the study (up to 20% of
enrolled patients in each Phase).

- Agree to effective contraception during the duration of the study with contraception
use for 14 months for female patients and 11 months for male patients after the last
dose of study treatment.

- Female patients of childbearing potential must have a negative serum pregnancy test at
Screening and agree to use highly effective methods of contraception throughout the
study and for 14 months following the last dose of study treatment (except patients
with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year,
or previous bilateral salpingo-oophorectomy, or hysterectomy).

- Male patients who are sexually active must use highly effective methods of
contraception throughout the study and for 11 months following the last dose of study
treatment. Male patients must agree not to donate sperm during the study treatment
period and for 11 months following the last dose of study treatment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

- DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma
(Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases
other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL);
T-cell rich large B-cell lymphoma.

- Previous treatment with selinexor or other XPO1 inhibitors.

- Contraindication to any drug contained in the combination therapy regimen (SR-GDP).

- Known active central nervous system or meningeal involvement by DLBCL at time of
Screening.

- Use of any standard or experimental anti-DLBCL therapy (including nonpalliative
radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer
therapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted;
palliative radiation is permitted only if on non-target lesions).

- Any AE, by C1D1, which has not recovered to Grade =1 (Common Terminology Criteria for
Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL
therapy, except alopecia.

- Major surgery <14 days of Cycle 1 Day 1.

- Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to
C1D1 or active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot
discontinue GVHD treatment or prophylaxis) or CAR-T cell infusion <90 days prior to
Cycle 1.

- Neuropathy Grade =2 (CTCAE, v.5.0).

- Any life-threatening illness, medical condition, or organ system dysfunction which, in
the Investigator's opinion, could compromise the patient's safety, or being compliant
with the study procedures.

- Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,
antivirals, or antifungals within 7 days prior to first dose of study treatment;
however, prophylactic use of these agents is acceptable (including parenteral).

- Patient with active hepatitis B, hepatitis C or HIV infections. Patient with a history
of hepatitis B, hepatitis C or HIV are allowed under the following conditions: Patient
with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B
has been given for >8 weeks and viral load is <100 International units (IU)/mL prior
to first dose of study treatment. Patient with untreated hepatitis C virus (HCV) are
allowed if there is documentation of negative viral load per institutional standard.
Patient with human immunodeficiency virus (HIV) who have CD4+ T-cell counts =350
cells/microliter (µL), negative viral load per institutional standard, and no history
of acquired immune deficiency syndrome (AIDS) -defining opportunistic infections in
the last year are allowed.

- Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal
(GI) disease or dysfunction that could interfere with absorption of study treatment.

- Breastfeeding or pregnant women.

- Inability or unwillingness to sign an informed consent form (ICF).

- In the opinion of the Investigator, patient who are significantly below their ideal
body weight.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St. Vincent's Health Network, Kinghorn Cancer Centre - Sydney
Recruitment hospital [2] 0 0
Eastern Health - Box Hill
Recruitment hospital [3] 0 0
St Vincent's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3065 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New Mexico
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Austria
State/province [12] 0 0
Linz
Country [13] 0 0
Austria
State/province [13] 0 0
Vienna
Country [14] 0 0
France
State/province [14] 0 0
Bordeaux
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Germany
State/province [16] 0 0
Bavaria
Country [17] 0 0
Germany
State/province [17] 0 0
Bayern
Country [18] 0 0
Germany
State/province [18] 0 0
Hessen
Country [19] 0 0
Germany
State/province [19] 0 0
Rhineland-Palatinate
Country [20] 0 0
Germany
State/province [20] 0 0
Dresden
Country [21] 0 0
Germany
State/province [21] 0 0
Hamburg
Country [22] 0 0
Israel
State/province [22] 0 0
Ashdod
Country [23] 0 0
Israel
State/province [23] 0 0
Beer Sheva
Country [24] 0 0
Israel
State/province [24] 0 0
Haifa
Country [25] 0 0
Israel
State/province [25] 0 0
Holon
Country [26] 0 0
Israel
State/province [26] 0 0
Jerusalem
Country [27] 0 0
Israel
State/province [27] 0 0
Petach Tikva
Country [28] 0 0
Israel
State/province [28] 0 0
Tel aviv
Country [29] 0 0
Israel
State/province [29] 0 0
Tel Aviv
Country [30] 0 0
Italy
State/province [30] 0 0
Napoli
Country [31] 0 0
Italy
State/province [31] 0 0
Sicilia
Country [32] 0 0
Italy
State/province [32] 0 0
Torino
Country [33] 0 0
Italy
State/province [33] 0 0
Ancona
Country [34] 0 0
Italy
State/province [34] 0 0
Bologna
Country [35] 0 0
Italy
State/province [35] 0 0
Caserta
Country [36] 0 0
Italy
State/province [36] 0 0
Novara
Country [37] 0 0
Italy
State/province [37] 0 0
Rome
Country [38] 0 0
Poland
State/province [38] 0 0
Lesser
Country [39] 0 0
Poland
State/province [39] 0 0
Pomerania
Country [40] 0 0
Poland
State/province [40] 0 0
Wielkopolska
Country [41] 0 0
Poland
State/province [41] 0 0
Warsaw
Country [42] 0 0
Poland
State/province [42] 0 0
Warszawa
Country [43] 0 0
Spain
State/province [43] 0 0
Badalona
Country [44] 0 0
Spain
State/province [44] 0 0
Barcelona
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Seville
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Co Antrim
Country [48] 0 0
United Kingdom
State/province [48] 0 0
North West England
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Karyopharm Therapeutics Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of
selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive
hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T)
therapy. The Phase 2 portion of the study will assess the two doses of selinexor (40
milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle),
followed by 60 mg selinexor single agent continuous therapy for those who have reached a
partial or complete response. The Phase 3 portion of the study will evaluate the selected
dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6
cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous
therapy for those who have reached partial or complete response.
Trial website
https://clinicaltrials.gov/show/NCT04442022
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jatin Shah Chief Medical Officer, MD
Address 0 0
Country 0 0
Phone 0 0
(617) 658-0600
Fax 0 0
Email 0 0
jshah@karyopharm.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04442022