Sonntag, 13. Juni 2021
Navigation öffnen
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:
20.05.2021

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

Sharon Shacham Chief Scientific Officer, PhD
Kontakt:
Phone: (617) 658-0600
E-Mail: sshacham@karyopharm.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 49)

Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers
85224 Chandler
United StatesNoch nicht rekrutierend» 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 StatesNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Ruemu Birhiray, MD
Phone: 317-297-2208
E-Mail: rbirhiraymd@investigativeicr.com
» Ansprechpartner anzeigen
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 StatesRekrutierend» Google-Maps
Ansprechpartner:
Henry Igid, MD
Phone: +1 702-24-7200
E-Mail: henry.igid@usoncology.com
» Ansprechpartner anzeigen
New Mexico Cancer Care Alliance
87106 Albuquerque
United StatesNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Leslie A Andritsos, MD
Phone: 505-925-0405
E-Mail: landritsos@salud.unm.edu
» Ansprechpartner anzeigen
Texas Oncology - Presbyterian Dallas Cancer Center
75231 Dallas
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Kristi McIntyre, MD
Phone: 214-739-4175
E-Mail: kristi.mcintyre@usoncology.com
» Ansprechpartner anzeigen
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
Kepler Universitaetskrankenhaus Med Campu III - Onkologie
4021 Linz
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Clemens Schmitt, MD
Phone: +43 5 768 083 6204
E-Mail: clemens.schmitt@kepleruniklinikum.at
» Ansprechpartner anzeigen
University of Vienna, Medical Clinic I, Hematology
1090 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Ulrich Jaeger, MD
Phone: +43 1 404 004 4100
E-Mail: ulrich.jaeger@meduniwien.ac.at
» Ansprechpartner anzeigen
Rambam health care campus (Department of Hematology & Bone Marrow Transplantation)
3109601 Haifa
IsraelRekrutierend» Google-Maps
Ansprechpartner:
Shimrit Ringelstein-Harlev, MD
Phone: +972 4 777 3705
E-Mail: s_ringelstein@rambam.health.gov.il
» Ansprechpartner anzeigen
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
ItalyNoch nicht rekrutierend» 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
ItalyNoch nicht rekrutierend» 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
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
PolandNoch nicht rekrutierend» 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
8916 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. 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.

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 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.

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.

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 (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))

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 (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))

4. Phase 3: Overall Survival (OS) (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 (ORR-EoC): 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: Progression-free Survival (PFS): 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))

9. 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))

10. Phase 3: 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)

11. Phase 3: Overall Response Rate at the End of Combination Therapy (ORR-EoC): 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)

12. Phase 3: 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))

13. Phase 3: Progression-free Survival (PFS): 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))

14. Phase 3: 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))

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


Das könnte Sie auch interessieren
Darmkrebspatienten benötigen spezialisierte Anlaufstelle und Interessenvertretung
Darmkrebspatienten+ben%C3%B6tigen+spezialisierte+Anlaufstelle+und+Interessenvertretung
© Fotolia / cryonoid_media

Mit einem Pressegespräch am 19. April in Berlin nimmt EuropaColon Deutschland e. V. seine Tätigkeit als spezialisierte Anlaufstelle und Interessenvertretung von Darmkrebspatienten auf. Der neu gegründete Verein ist die deutsche Tochter der seit zwölf Jahren europaweit aktiven Patientenorganisation EuropaColon, die in 24 Ländern Europas Menschen mit Darmkrebs unterstützt und gegenüber der Gesundheitspolitik für deren...