A Phase III, Randomized, Open-label, Clinical Trial to Compare Pembrolizumab with Brentuximab Vedotin in Subjects with Relapsed or Refractory Classical Hodgkin Lymphoma
Michelle A. Fanale
The goal of this clinical research study is to learn if pembrolizumab (MK-3475) can help to control the disease better than brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma. The safety of these drugs will also be studied.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: Brentuximab Vedotin,Pembrolizumab
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Merck Sharp & Dohme Corp.
Primary Objective: 1. To compare PFS (Progression free Survival) as assessed by blinded independent central review according to the IWG (International Working Group) response criteria between treatment arms. 2. To compare OS (overall survival) between treatment arms. The study is considered to have met its primary objective if pembrolizumab is superior to brentuximab vedotin in either PFS or OS. Secondary Objective: 1. To compare the objective response rate (ORR) as assessed by blinded independent central review according to the IWG response criteria between treatment arms. 2. To determine the duration of response (DOR) as assessed by blinded independent central review and investigator assessment according to the IWG response criteria by treatment arm. 3. To compare ORR as assessed by blinded independent central review according to the IWG response criteria for subjects with pre-pembrolizumab PD-L1 positive versus PD-L1 negative lymphoid tumors 4. To explore the relationship between genomic variation and response to the treatment(s) administered. Variation across the human genome (tumor and germline) will be analyzed for association with clinical data collected in this study 5. To compare the changes from baseline between the treatment arms in health-related quality-of-life assessments using the EORTC QLQ-C30 and EuroQol EQ-5D. 6.To evaluate ORR, CRR, and DOR as assessed by blinded independent central review according to the Lugano criteria by treatment arm. 7.To evaluate PFS as assessed by the investigator according to the IWG response criteria by treatment arm. 8. To evaluate PFS after auto-SCT, as assessed by the investigator and by blinded independent central review, according to the IWG response criteria by treatment arm. 9. To evaluate the toxicity profiles as graded by the investigator according to CTCAE, version 4.0 by treatment arm.
IRB Review and Approval Date: 08/01/2016
Recruitment Status: Open
Projected Accrual: 300
1) Be willing and able to provide written informed consent for the trial
and adhere to trial procedures. The subject may also provide consent for
Future Biomedical Research. However, the subject may participate in the
main trial without participating in Future Biomedical Research.
2) Be >/= 18 years of age on day of signing informed consent.
3) Have relapsed (disease progression after most recent therapy) or refractory (failure to achieve CR or PR to most recent therapy) classical HL.
4) Have responded (achieved a CR or PR) to BV or BV-containing regimens, if previously treated with BV. (Note: Prior treatment with BV or BV-containing regimens is allowed, but not required.)
5) Have measureable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral computed tomography (CT) scan or combined CT/positron emission tomography (PET) scan. Minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis.
6) Be able to provide an evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening (Visit 1).
7) Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
8) Demonstrate adequate organ function including ANC >/= 1, platelets >/= 75,000, Hgb > 8.
9) Female subjects of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
10) Female subjects of childbearing potential must be willing to use an adequate method of contraception. Contraception for the course of the study through 120 days (for subjects receiving pembrolizumab) or 180 days (for subjects receiving BV) after the last dose of study medication.
11) Male subjects of childbearing potential must be willing to use an adequate method of contraception.
1) Has severe (>/= Grade 3) hypersensitivity to the active substance
or to any of the excipients in BV or pembrolizumab.
2) Is currently participating in or has participated in a study of an investigational agent and is currently receiving study therapy or has participated in a study of an investigational agent and has received study therapy or used an investigational device within 4 weeks of the first dose of treatment. Note: Subjects who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks since the last dose of the previous investigational treatment.
3) Has a diagnosis of immunosuppression or is receiving systemic steroid therapy (exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
4) Has had a prior monoclonal antibody within 4 weeks prior to first dose of therapy in the study or who has not recovered (i.e., </= Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier.
5) Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy including investigational agents within 4 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from AEs due to a previously administered agent. -Note: If a subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
6) Has undergone prior allogeneic stem cell transplantation within the last 5 years. - Note: Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft-versus-host disease (GVHD).
7) Has a known additional malignancy that is progressing or has required active treatment in the last 3 years. -Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
8) Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (ie. without evidence of progression for at least 4 weeks by repeat imaging (note that the repat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of trial treatment.
9) Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with the use of disease modifying agents, corticosteroids, or immunosuppressive drugs -Note: 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.
10) Has history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
11) Has an active infection requiring intravenous systemic therapy.
12) Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
13) Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment.
14) Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, CTLA - 4 antibody (including ipilimumab), or OX-40, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
15) Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
16) Has active hepatitis B (HBV) (e.g., HBsAg reactive) or hepatitis C (HCV) (e.g., HCV RNA [qualitative] is detected). Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
17) Has received a live vaccine within 30 days prior to first dose.
18) Has a known history of active turberculosis (TB; Bacillus turberculosis).
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
Michelle A. Fanale
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