Pembrolizumab and Brentuximab Vedotin vs GDP and Stem Cell Transplant for Relapsed/Refractory Hodgkin Lymphoma

Sponsor
Canadian Cancer Trials Group (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05180097
Collaborator
Merck Sharp & Dohme Corp. (Industry), Seagen Inc. (Industry)
84
Enrollment
2
Arms
39
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study is being done to determine if two new drugs can shrink or eliminate classical Hodgkins lymphoma.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

Treatment given to patients whose disease has not responded to (refractory) or returned (relapsed) after previous treatment is known as salvage treatment.

The standard of care for patients who are not in a study is salvage treatment with gemcitabine, dexamethasone and cisplatin (GDP). This treatment can reduce symptoms and may stop the lymphoma from growing for a few months or longer. This standard treatment is approved by Health Canada

We are doing this study because we want to find out if treatment with Pembrolizumab and Brentuximab vedotin is better or worse than the standard of care for this type of cancer, classical Hodgkin lymphoma. The standard of care is defined as care most people get for your cancer.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Study of Pembrolizumab and Brentuximab Vedotin Versus GDP, Followed by High Dose Chemotherapy and Autologous Stem Cell Transplantation for Relapsed/Refractory Classical Hodgkin Lymphoma
Anticipated Study Start Date :
Mar 30, 2022
Anticipated Primary Completion Date :
Jun 30, 2024
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: GDP

Drug: Gemcitabine
1000mg/m2 IV, 30 mins D1, D8

Drug: Dexamethasone
40mg daily PO, D1-D4

Drug: Cisplatin
75mg/m2 IV, 1 hour, D1

Active Comparator: Brentuximab vedotin + Pembrolizumab

Drug: Brentuximab vedotin
1.8 mg/kg IV, 30 mins, Q21 days

Drug: Pembrolizumab
200mg IV, 30 mins, Q 21 days

Outcome Measures

Primary Outcome Measures

  1. Complete response rate by PET Deauville criteria (score 1-3) of pembrolizumab and brentuximab vedotin compared to standard GDP (gemcitabine, dexamethasone, cisplatin) given as salvage therapy [52 months]

Secondary Outcome Measures

  1. Progression-free survival [52 months]

  2. Event-free survival [52 months]

  3. Overall survival [52 months]

  4. Successful stem cell collection rate [52 months]

  5. Transplantation rate [52 months]

  6. Number and severity of adverse events [52 months]

  7. Patient-reported Quality of Life utilizing EORTC QLQ-C30 [52 months]

  8. Patient-reported toxicity utilizing PRO-CTCAE [52 months]

  9. Patient-reported Quality of Life utilizing FACT-LYM evaluating symptoms and concerns associated specifically with the lymphoma disease and/or disease treatment. [52 months]

  10. Patient-reported Quality of Life utilizing FACT/GOG-Ntx-Subscale specifically with chemotherapy-induced neuropathy [52 months]

  11. Health Economics utilizing EQ-5D-5L [52 months]

  12. Health Economics financial toxicity utilizing FACIT-COST [52 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • History of classic Hodgkin lymphoma by histopathology and now have relapsed or refractory disease after anthracycline-containing chemotherapy and eligible for high dose chemotherapy and autologous stem cell transplant

  • 18 years of age or greater

  • ECOG performance status 0-1

  • Clinically and/or radiologically measurable disease as per the Lugano 2014 classification

  • Life expectancy > 90 days

  • Absolute neutrophils ≥1.0 x 109/L; Platelets ≥75 x 109/L; Hemoglobin ≥80 g/L: Bilirubin ≤1.50 x UNL; AST and ALT ≤2.50 x UNL; Serum creatinine <1.55 x UNL or Creatinine clearance ≥30 mL/min

  • Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires and/or health utility in either English or French

  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.

  • Patient must be accessible for treatment and follow-up. Patients enrolled on this trial must be treated and followed at the participating centre.

  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment

  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during the study plus approximately 6 months after treatment completion

  • All patients must have a tumour block from their primary diagnostic biopsy available and the centre/pathologist must have agreed to release the block or recently cut slides for correlative analysis if the patient has consented.

Exclusion Criteria:
  • Patients who have received prior salvage systemic therapy for their relapsed or refractory disease.

  • History of peripheral neuropathy or dyspnea ≥ grade 2

  • Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast, or localized excised prostate cancer, other solid tumours curatively treated with no evidence of disease for > 3 years

  • History of active CNS disease

  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at doses more than 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first and any dose of trial treatment

  • Has active autoimmune disease that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or history of allogeneic transplantation. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

  • Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus infection, active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients that are Hepatitis B core antibody positive are eligible if they are HBV DNA negative and are concurrently treated with anti-viral therapy. Patients with a past history of hepatitis C who have eradicated the virus are eligible

  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, angina, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification

  • Documented history of cerebral vascular event (stroke or transient ischemic attack)

  • History of progressive multifocal leukoencephalopathy (PML).

  • Any serious active disease or co-morbid medical condition, including psychiatric illness, judged by the local investigator to preclude safe administration of the planned protocol treatment or required follow-up

  • Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety (for example): active, uncontrolled bacterial, fungal or viral infection; clinically significant cardiac dysfunction or cardiovascular disease

  • Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of enrollment

  • Pregnant or lactating females, or women/men of childbearing potential not willing to use an adequate method of birth control for the duration of the study through 6 months after the last dose of trial treatment

  • Patients are not eligible if they have had a prior infusion reaction to the study drugs or their components > grade 2

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

  • Patient has had an allogenic tissue/solid organ transplant

  • Concurrent or within the previous 4 weeks, treatment with other investigational drugs or anti-cancer therapy

  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A one-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Canadian Cancer Trials Group
  • Merck Sharp & Dohme Corp.
  • Seagen Inc.

Investigators

  • Study Chair: Kerry Savage, BCCA-Vancouver Cancer Centre
  • Study Chair: John Kuruvilla, University Health Network, Princess Margaret Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Canadian Cancer Trials Group
ClinicalTrials.gov Identifier:
NCT05180097
Other Study ID Numbers:
  • HD11
First Posted:
Jan 6, 2022
Last Update Posted:
Mar 9, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 9, 2022