A Phase II Study of Pembrolizumab (MK-3475) in Subjects with Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) or Relapsed or Refractory Richter Syndrome (rrRS)
- Clements University Hospital
Syed Rizvi, M.D.
This is an open label, multicenter, single arm trial of pembrolizumab (MK-3475) in subjects with relapsed or refractory Primary Mediastinal Large B-Cell Lymphoma (rrPMBCL) who have failed to achieve a complete response (CR) or relapsed after autologous stem cell transplant (auto-SCT) or are ineligible for auto-SCT and have failed to respond or relapsed after [Greater Than]/[?] 2 lines of prior treatment. Subjects are required to submit for central review an
archive or fresh lymph node biopsy sample for confirmation of PMBCL diagnosis and screening PeT/CT scans for confirmation of measurable disease previous to entering the study.
approximately 53 subjects will be enrolled in this trial to examine the safety and efficacy of pembrolizumab 200 mg fixed dose administered Q3W.
Male/Female subjects with relapsed or refractory Primary Mediastinal Large B-cell lymphoma (PMBCL), of at least 18 years of age will be enrolled in this trial.
1. Be willing and able to provide written informed consent for the trial. 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. Confirmed diagnosis of Primary Mediastinal Large B-cell lymphoma by independent central pathology review, according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues (WHO Criteria, 2008 ). Subject must be able to provide an evaluable core or excisional lymph node biopsy for confirmation of PMBCL diagnosis from an archival or newly obtained
lymph node biopsy at Screening. In addition subjects may be asked to provide additional biopsy samples, if possible, at Week 12 and at the time of discontinuation due to progression for biomarker analysis.
4. Have relapsed*a or refractory*b Primary Mediastinal Large B-cell lymphoma and:
Have relapsed after auto-SCT or have failed to achieve a Complete Response within 60 days of auto-SCT. Subjects may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment.
For subjects who are ineligible for auto-SCT, have received at least >= 2 lines of prior therapy and have failed to respond to or relapsed after their last line of treatment. For subjects who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of treatment.
a) Relapsed Disease: progression of disease after achieving a remission to the most recent therapy
b) Refractory Disease: failure to achieve CR to the most recent therapy
5. Must have been previously exposed to rituximab as part of prior lines of treatment.
6. Pathologic diagnosis per local institutional review of Richter syndrome that transformed from CLL.
7. Have relapsed or refractory Richters syndrome and has received at least 1 previous treatment for RS.
8. Have radiographically measureable disease by independent central review, defined as at least one lesion that can be accurately measured in at least two dimensions with spiral computed tomography (CT) scan. Minimum measurement must be > 15 mm in the longest diameter.
a. RS subjects must also be PET positive at screening, defined as having at least one lesion, attributable to malignancy and with appropriate correlation to anatomic imaging, with uptake greater than that of normal liver tissue.
9. Must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
10. Life expectancy > 3 months
11. Must demonstrate adequate organ function as defined in Table 1(Page 27 of protocol); all screening labs should be performed within 7 days of treatment initiation.
12. Female subjects of childbearing potential should have a negative urine or serum pregnancy test 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.
13. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (see Section 5.7.2 page 39 of the protocol ). Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
14. Male subjects of childbearing potential (Section 5.7.2) must agree to use an adequate method of contraception as outlined in Section 5.7.2 x Contraception, starting with the first dose of study therapy through 120 days after the last dose of
study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.