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JOURNAL ONKOLOGIE – STUDIE

A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Rekrutierend

NCT-Nummer:
NCT04442022

Studienbeginn:
September 2020

Letztes Update:
21.03.2024

Wirkstoff:
Selinexor (combination therapy), Placebo matching for Selinexor (combination therapy), Rituximab (combination therapy), Gemcitabine (combination therapy), Dexamethasone (combination therapy), Cisplatin (combination therapy), Selinexor (continuous therapy), Placebo matching for Selinexor (continuous therapy)

Indikation (Clinical Trials):
Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Karyopharm Therapeutics Inc

Collaborator:
-

Kontakt

Studienlocations
(3 von 57)

Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers
85224 Chandler
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Sujith Kalmadi, MD
Phone: 480-821-2838
E-Mail: kalmadi@ironwoodcrc.com
» Ansprechpartner anzeigen
Investigative Clinical Research of Indiana, LLC
46260 Indianapolis
United StatesZurückgezogen» Google-Maps
Tulane Cancer Center
70112 New Orleans
United StatesZurückgezogen» Google-Maps
University of Maryland Greenebaum Comprehensive Cancer Center
21201 Baltimore
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Seung Tae Lee, MD
Phone: 410-328-8708
E-Mail: seunglee@umm.edu
» Ansprechpartner anzeigen
Comprehensive Cancer Centers of Nevada - Town Center
89169 Las Vegas
United StatesZurückgezogen» Google-Maps
New Mexico Cancer Care Alliance
87106 Albuquerque
United StatesZurückgezogen» Google-Maps
Gabrail Cancer Center Research LLC
44718 Canton
United StatesZurückgezogen» Google-Maps
Texas Oncology - Medical City Dallas
75230 Dallas
United StatesZurückgezogen» Google-Maps
Texas Oncology - Presbyterian Dallas Cancer Center
75231 Dallas
United StatesZurückgezogen» Google-Maps
Texas Oncology - Sammons
75246 Dallas
United StatesZurückgezogen» Google-Maps
Texas Oncology - Fort Worth
76104 Fort Worth
United StatesZurückgezogen» Google-Maps
Texas Oncology - Plano East
75075 Plano
United StatesZurückgezogen» Google-Maps
The University of Texas Health Science Center at Tyler DBA UT Health East Texas HOPE Cancer Center
75702 Tyler
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Marc Usrey, MD
Phone: 903-595-7044
E-Mail: Marc.Usrey@uthct.edu
» Ansprechpartner anzeigen
Providence Regional Cancer Partnership
98201 Everett
United StatesZurückgezogen» Google-Maps
Kepler Universitaetskrankenhaus Med Campu III - Onkologie
4021 Linz
AustriaZurückgezogen» Google-Maps
University of Vienna, Medical Clinic I, Hematology
1090 Vienna
AustriaZurückgezogen» Google-Maps
The First Affiliated Hospital of Soochow University
215006 Suzhou
ChinaAbgeschlossen» Google-Maps
Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School
200025 Huangpu
ChinaAbgeschlossen» Google-Maps
Zhongshan Hospital Fudan University
200032 Xuhui District
ChinaAbgeschlossen» Google-Maps
Huaxi Hospital Sichuan University
610044 Chengdu
ChinaAbgeschlossen» Google-Maps
The first affiliated Hospital, Zhejiang University
310003 Hangzhou
ChinaAbgeschlossen» Google-Maps
Rambam health care campus (Department of Hematology & Bone Marrow Transplantation)
3109601 Haifa
IsraelZurückgezogen» Google-Maps
Hadassah Medical Center
9103401 Jerusalem
IsraelZurückgezogen» Google-Maps
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
90146 Palermo
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Caterina Patti, MD
Phone: +39 91 780 2037
E-Mail: k.patti@ospedaliriunitipalermo.it
» Ansprechpartner anzeigen
AOU Ospedali Riuniti-Università Politecnica delle Marche Clinica di Ematologia
60020 Ancona
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Guido Gini, MD
Phone: +39 71 596 4562/4235
E-Mail: guido.gini@ospedaliriuniti.marche.it
» Ansprechpartner anzeigen
AOU Policlinico S.Orsola Malpighi di Bologna, University of Bologna
40138 Bologna
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Pier Luigi Zinzani, MD
Phone: +39 51 214 3680
E-Mail: pierluigi.zinzani@unibo.it
» Ansprechpartner anzeigen
UOC Ematologia ad Indirizzo Oncologico, AORN "Sant'Anna e San Sebastiano"
81100 Caserta
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Ferdinando Frigeri, MD
Phone: +39 82 323 2192
E-Mail: ferdinando.frigeri@aorncaserta.it
» Ansprechpartner anzeigen
DIP. Oncologia- Ematologia, UOSD Centro Diagnosie TerapiaDei Linfomi
65124 Pescara
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Elsa Pennese, MD
Phone: +39 347 307 9075
E-Mail: elsapennese@gmail.com
» Ansprechpartner anzeigen
Szpitale pomorskie gdynia dept of haematology
81-519 Gdynia
PolandRekrutierend» Google-Maps
Ansprechpartner:
Wanda Knopinska-Posluszny, MD
Phone: +48 58 726 0570
E-Mail: wanda.knopinska@gmail.com
» Ansprechpartner anzeigen
Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wrocławiu
50-367 Wroclaw
PolandRekrutierend» Google-Maps
Ansprechpartner:
Tomasz Wrobel
E-Mail: tomasz_wrobel@wp.pl
» Ansprechpartner anzeigen
Institute of Hematology and Transfusion Medicine
00-791 Warsaw
PolandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Ewa Lech-Maranda, MD
Phone: 48223496454
E-Mail: emaranda@ihit.waw.pl
» Ansprechpartner anzeigen
Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology
02-781 Warszawa
PolandRekrutierend» Google-Maps
Ansprechpartner:
Jan Walewski, MD
Phone: +48 22 546 3248
E-Mail: jan.walewski@pib-nio.pl
» Ansprechpartner anzeigen
Institut català d'oncologia-hospital germans trias i pujol
08916 Badalona
SpainRekrutierend» Google-Maps
Ansprechpartner:
Juan Manuel Sancho, MD
Phone: +34 93 497 8987
E-Mail: jsancho@iconcologia.net
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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. This study consists of 3 arms each in Phase 2 and 3. 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. 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.

Ein-/Ausschlusskriterien

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 3 prior lines of systemic therapy for the

treatment of DLBCL with relapsed or refractory disease following their most recent

regimen.

- 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). The Deauville 5-point scale

(D5PS) score assessed on the FDG PET/CT should be between 3 to 5.

- 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 approximately 15 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:

- 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:

- 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.

- Agree to highly effective contraception during the duration of the study with

contraception use continuing for 12 months 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 12 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 12 months following the last dose of study

treatment. Male patients must agree not to donate sperm during the study treatment

period and for 12 months following the last dose of study treatment.

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 hematological abnormalities (as specified in the inclusion criteria)

and alopecia.

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

- Hematopoietic stem cell transplantation/CAR-T therapy as follows:

- Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior

to C1D1

- Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot

discontinue GVHD treatment or prophylaxis)

- 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 virus (HBV), hepatitis C virus (HCV), or human

immunodeficiency virus (HIV) infections:

- Patient with active HBV 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.

- Patients with known history of HCV or found to be HCV antibody positive on

screening, are allowed if there is documentation of negative viral load per

institutional standard.

- Patients with HIV are allowed if they have a negative viral load per

institutional standard, and no history of acquired immune deficiency syndrome

(AIDS)-defining opportunistic infections in the last year.

- 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.

- Patients who received a live attenuated vaccine within prior 28 days of the first dose

of study treatment.

Studien-Rationale

Primary outcome:

1. Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014 (Time Frame - From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization))

2. Phase 3: Progression-free Survival (PFS): Based on Lugano Criteria 2014 (Time Frame - From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization))

Secondary outcome:

1. Phase 2: Progression-free Survival: Based on Lugano Criteria 2014 (Time Frame - From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization))

2. Phase 2: Overall Survival (OS) (Time Frame - From date of initial randomization until death (maximum of 5 years from randomization))

3. Phase 3: Overall Response Rate: Based on Lugano Criteria 2014 (Time Frame - From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization))

4. Phase 3: Overall Survival (Time Frame - From date of initial randomization until death (maximum of 5 years from randomization))

5. Phase 2: Overall Response Rate at the End of Combination Therapy (ORR-EoC): Based on Lugano Criteria 2014 (Time Frame - From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy)

6. Phase 2: Overall Response Rate at the End of Combination Therapy: Based on Modified Lugano Criteria (Time Frame - From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy)

7. Phase 2: Duration of Response (DOR): Based on Lugano Criteria 2014 (Time Frame - From time of first response until disease progression or death (maximum of 5 years from randomization))

8. Phase 2: Number of Patients with Adverse Events (AEs) (Time Frame - Up to 30 days after last dose of study drug (maximum of 5 years from randomization))

9. Phase 3: Overall Response Rate at the End of Combination Therapy: Based on Lugano Criteria 2014 (Time Frame - From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy)

10. Phase 3: Overall Response Rate at the End of Combination Therapy: Based on Modified Lugano Criteria (Time Frame - From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy)

11. Phase 3: Duration of Response: Based on Lugano Criteria 2014 (Time Frame - From time of first response until disease progression or death (maximum of 5 years from randomization))

12. Phase 3: Progression-free Survival: Based on Modified Lugano Criteria (Time Frame - From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization))

13. Phase 3: Number of Patients with Adverse Events (Time Frame - Up to 30 days after last dose of study drug (maximum of 5 years from randomization))

Studien-Arme

  • 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.

Geprüfte Regime

  • 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
  • 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
  • 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
  • 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
  • Rituximab (combination therapy):
    Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)
  • Rituximab (combination therapy):
    Dose: 375 mg/m^2 on Day 1; Route of administration: IV
  • Gemcitabine (combination therapy):
    Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV
  • 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
  • Cisplatin (combination therapy):
    Dose: 75 mg/m^2 on Day 1; Route of administration: IV
  • Selinexor (continuous therapy):
    Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
  • 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

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma"

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