A Phase II Study of the Combination of Pembrolizumab and ATRA Combination Treatment of Relapsed HL and B-NHL

Inclusion Criteria

• •1. ≥ 18 years old at the time of informed consent
• •2. Ability to provide written informed consent and HIPAA authorization
• •3. Willingness to comply with all study procedures and be available for the duration of the trial
• •4. Have a performance status of 0 to 2 on the ECOG Performance Scale.
• •5. Life expectancy ≥12 weeks as per investigator discretion
• •6. Patients with histologically proven, relapsed or refractory HL or B-NHL as follows:
• •1. HL after failure of at least 1 prior line of systemic therapy
• •2. Primary mediastinal large B-cell lymphoma (PMBCL) that is refractory to first-line therapy
• •3. Other B-cell NHLs after failure of at least 2 prior lines of systemic therapy. The eligible types of B-cell NHLs are:
• •7. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 10 days prior to the first study treatment: Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) INR and aPTT ≤1.5 x ULN; this applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. Renal calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) calculated creatinine clearance ≥ 60 mL/min Hepatic Serum total bilirubin
• •* 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN (patients with known Gilbert disease who have bilirubin levels ≤ 3 x ULN may be enrolled). Patients must be able to undergo biliary stenting if required before or, if required, during the trial AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
• •* 5 X ULN for subjects with liver metastases Albumin \>2.5 mg/dL
• •8. Female subject of childbearing potential should 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. Note: Female of childbearing potential definition: (ECOG definition) Any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• •1. Has not undergone a hysterectomy or bilateral oophorectomy; or
• •2. Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• •9. Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
• •Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• •Refer to section 8.4.1 for more information.
• •10. Male subjects of childbearing potential must agree to use an adequate method of contraception of the protocol, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Refer to section 8.4.1 for more information.
• •11. Acceptable methods of contraception include IUD, oral contraceptive, subdermal implant, and double barrier (condom with a contraceptive sponge or contraceptive pessary). Micro-dosed progesterone preparations ("mini-pill") are an inadequate method of contraception during treatment with ATRA. If patients are taking this pill they should be instructed to stop, and another form of contraceptive should be prescribed instead.
• •10. Patient has undergone major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day -1 of treatment in this study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• •11. Known history of, or any evidence of active, non-infectious pneumonitis.
• •12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• •13. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •14. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •15. 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 after the last dose of trial treatment.
• •16. Patients on micro-dosed progesterone preparations ("mini-pill") who are unwilling to receive an alternative form of contraception.
• •17. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• •18. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• •19. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• •20. known history of active TB (Bacillus Tuberculosis).
• •21. Receipt of live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• •22. Patients who receive a COVID shot and/or booster within 4 weeks of Cycle 1 Day -1.
• •23. Known sensitivity to retinoic acid derivatives.
• •24. Patient is taking any prohibited concurrent medication, including Vitamin A supplements, and CYP3A modulators (inducers and inhibitors) and is unwilling to stop use (washout period of 3 days for this protocol) prior to treatment start and during the trial.
• •25. History of allogenic stem cell transplant or received a solid organ transplant. Note: If history of transplant is ≥ 5 years, subjects may be deemed eligible at the discretion of the treating physician. Note: Patients with a history of autologous stem cell transplant performed for lymphoma are eligible.