Freitag, 5. März 2021
Navigation öffnen
Anzeige:
Keytruda Pantumor
Keytruda Pantumor
JOURNAL ONKOLOGIE – STUDIE

Safety and Efficacy of Pembrolizumab (MK-3475) in Children and Young Adults With Classical Hodgkin Lymphoma (MK-3475-667/KEYNOTE-667)

Rekrutierend

NCT-Nummer:
NCT03407144

Studienbeginn:
April 2018

Letztes Update:
01.03.2021

Wirkstoff:
Pembrolizumab, Doxorubicin, Vinblastine, Dacarbazine, Cyclophosphamide, Vincristine, prednisone/prednisolone, Bleomycin, Etoposide

Indikation (Clinical Trials):
Lymphoma, Hodgkin Disease

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Phase 2

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations (3 von 69)

Memorial Regional Hospital/Joe DiMaggio Children's Hospital ( Site 0048)
33021 Hollywood
United StatesAbgeschlossen» Google-Maps
Severance Hospital Yonsei University Health System ( Site 0221)
03722 Seoul
Korea, Republic ofAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Group 1 will consist of low-risk participants with cHL Stages IA, IB and IIA without bulky

disease. Group 2 will consist of high-risk participants with cHL Stages IIEB, IIIEA, IIIEB,

IIIB, IVA and IVB.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Group 1: Must have newly diagnosed, pathologically confirmed cHL at Stages IA, IB and

IIA without bulky disease. Group 2: Must have newly diagnosed, pathologically

confirmed cHL at Stages IIEB, IIIEA,IIIEB, IIIB, IVA and IVB

- Has measurable disease per investigator assessment

- Male participants must agree to use approved contraception during the treatment period

and for at least 120 days (or longer, if required by the drug label of chemotherapy

received by the participant on study) after the last dose of study treatment and

refrain from donating sperm during this period

- Female participants who are not pregnant or breastfeeding, and who are either not a

woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved

contraception during the treatment period and for at least 120 days (or longer, if

required by the drug label of chemotherapy received by the participant on study) after

the last dose of study treatment

- Performance status: Lansky Play-Performance Scale ≥50 for children up to and including

16 years of age OR Karnofsky score ≥50 for participants >16 years of age

- Has adequate organ function

Exclusion Criteria:

- Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic

stem cell transplantation within the last 5 years

- WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of

study treatment

- Baseline left ventricular ejection fraction value <50% or shortening fraction of <27%

- Has received prior therapy with an anti-Programmed Death (PD)-1, anti-Programmed

Death-Ligand 1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another

co-inhibitory T-cell receptor or has previously participated in a Merck pembrolizumab

(MK-3475) clinical study

- Has received any prior anti-cancer therapy, monoclonal antibody, chemotherapy, or an

investigational agent or device before the first dose of study treatment, or has not

recovered from AEs due to previously administered agents

- Has received a live vaccine within 30 days prior to the first dose of pembrolizumab

- Is currently participating in or has participated in a study of an investigational

agent or has used an investigational device within 4 weeks prior to the first dose of

study treatment

- Has a diagnosis of lymphocyte-predominant Hodgkin Lymphoma (HL)

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

or any other form of immunosuppressive therapy within 7 days prior to the first dose

of pembrolizumab

- Has a known additional malignancy that is progressing or requires active treatment

- Has radiographically detectable central nervous system metastases and/or carcinomatous

meningitis as assessed by local site investigator at the time of diagnosis

- Has severe hypersensitivity (≥Grade 3) to any study therapies including any excipients

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a history of (non-infectious) pneumonitis that required steroids or has current

pneumonitis

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of Hepatitis B or known active Hepatitis C virus infection

- Has a known history of active tuberculosis

- Has a history or current evidence of any condition, therapy, or laboratory abnormality

that might confound the results of the study, interfere with the participant's

participation for the full duration of the study, or is not in the best interest of

the participant to participate, in the opinion of the treating investigator

- Has known psychiatric or substance abuse disorders that would interfere with

cooperating with the requirements of the study

- Is pregnant or breastfeeding or expecting to conceive or father children within the

projected duration of the trial, starting with the screening visit through 120 days

(or longer, if required by the drug label of chemotherapy received by the participant

on study) after the last dose of trial treatment

Studien-Rationale

Primary outcome:

1. Objective Response Rate (ORR) in SER Participants By Risk Group (Low, High) as Assessed by Blinded Independent Central Review (BICR) (Time Frame - Up to 5 years):
ORR is defined as the percentage of SER participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) using IWG revised response criteria and determined by BICR. The ORR will be estimated by risk group in SER participants.



Secondary outcome:

1. Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD or COPDAC-28 Chemotherapy (Time Frame - Up to 5 years):
The rate of PET negativity for SER participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of AVD (Group 1) or four cycles of COPDAC-28 (Group 2), in combination with pembrolizumab. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.

2. Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR (Time Frame - Up to 5 years):
EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by BICR using IWG criteria.

3. Overall Survival (OS) in SER Participants By Risk Group (Low, High) (Time Frame - Up to 5 years):
OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.

4. Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High) (Time Frame - Up to 5 years):
The frequency of RT received by eligible participants (positive PET response, i.e. Deauville score of 4 or 5) will be reported.

5. Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy (Time Frame - Up to 5 years):
The rate of PET negativity for Group 1 participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of ABVD induction. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the FDG avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.

6. EFS in Rapid Early Responder (RER) Participants By Risk Group (Low, High) as Assessed by Investigator (Time Frame - Up to 5 years):
EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by the investigator.

7. OS in RER Participants By Risk Group (Low, High) (Time Frame - Up to 5 years):
OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.

8. Serum Thymus and Activation-Regulated Chemokine (TARC) Levels in SER Participants By Risk Group (Low, High) (Time Frame - Up to 5 years):
Serum TARC levels will be measured and evaluated as a potential biomarker in SER participants by risk group at screening, early, and late response assessments.

9. Number of SER Participants Experiencing an Adverse Event (AE) By Risk Group (Low, High) (Time Frame - Up to 5 years):
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of SER participants who experience an AE will be reported for each arm.

10. Number of SER Participants Discontinuing Study Treatment Due to AEs By Risk Group (Low, High) (Time Frame - Up to 5 years):
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of SER participants who discontinue study treatment due to an AE will be reported for each arm.

Studien-Arme

  • Experimental: Pembrolizumab + AVD (Group 1)
    After receiving two 4-week cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) induction therapy, SER participants in Group 1 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) on Day 1 of each 3-week cycle (Q3W) in combination with two cycles of AVD chemotherapy (doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2 and dacarbazine 375 mg/m^2 on Days 1 and 15; cycle frequency every 4 weeks [Q4W]). All SERs in Group 1 will receive radiotherapy (RT) after completing AVD chemotherapy.
  • Experimental: Pembrolizumab + COPDAC-28 (Group 2)
    After receiving two 4-week cycles of OEPA (vincristine, etoposide/etopophos, prednisone/prednisolone and doxorubicin) induction therapy, SER participants in Group 2 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) Q3W, in combination with 4 cycles of COPDAC-28 chemotherapy (cyclophosphamide 500 mg/m^2 on Days 1 and 8, vincristine 1.5 mg/m^2 with maximum single dose 2 mg on Days 1 and 8, prednisone/prednisolone 40 mg/m^2/day divided in 3 doses on Days 1 to 15, dacarbazine 250 mg/m^2 on Days 1 to 3; cycle frequency Q4W). SERs in Group 2 will receive RT if they have a positive Positron Emission Tomography (PET) response after completing COPDAC-28 chemotherapy.

Geprüfte Regime

  • pembrolizumab (MK-3475):
    2 mg/kg intravenous (IV) up to a max of 200 mg (3 to 17 years of age) or 200 mg IV (18 to 25 years of age); cycle frequency Q3W
  • doxorubicin:
    25 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 40 mg/m^2 IV on Days 1 and 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 25 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1)
  • vinblastine:
    6 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 6 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1)
  • dacarbazine:
    375 mg/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 375 mg/m^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1) 250 mg/m^2 IV on Days 1 to 3 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)
  • cyclophosphamide:
    500 mg/m^2 IV on days 1 and 8 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)
  • vincristine:
    1.5 mg/m^2 IV with maximum single dose 2 mg on Days 1, 8, and 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 1.5 mg/m^2 IV with maximum single dose 2 mg on Days 1 and 8 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)
  • prednisone/prednisolone:
    60 mg/m^2/day orally divided in 3 doses on Days 1 to 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 40 mg/m^2/day orally divided in 3 doses on Days 1 to 15 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)
  • bleomycin:
    10 units/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1)
  • etoposide (Etoposide Phosphate):
    125 mg/m^2 IV on Days 1 to 5 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2)
  • Radiotherapy (RT):
    RT administered daily, dose dependent on randomization group and disease response.

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren

Wacken & DKMS: Gemeinsam gegen Blutkrebs

Wacken & DKMS: Gemeinsam gegen Blutkrebs
© DKMS gemeinnützige GmbH

Die DKMS ist zum vierten Mal mit einer Registrierungsaktion Teil des Wacken Open Air Festivals (W:O:A). Vom 3. bis zum 5. August 2017 können sich Besucher nicht nur über die lebensrettende Arbeit der internationalen gemeinnützigen Organisation informieren sondern sich auch als potenzielle Spender aufnehmen lassen. Parallel sind die Unterstützerinnen der Initiative „Wacken hilft“ mit viel Herzblut im Einsatz und verkaufen im Ort selbst gebackenen Kuchen zugunsten der DKMS...

Heller Hautkrebs: Signalweg entschlüsselt

Beim Hautkrebs gibt es verschiedene Krankheitsformen: Mit Abstand am häufigsten ist dabei das so genannte Basalzellkarzinom, eine Form von hellem Hautkrebs, bei der sich der Tumor von seinem Entstehungsort in der Haut langsam aber stetig ausbreitet. Zwar bildet das Basalzellkarzinom im Allgemeinen keine Tochtergeschwülste (Metastasen), der Tumor sollte jedoch so früh wie möglich behandelt werden, da er ansonsten das umgebende Gewebe zerstören und sogar Muskeln...