PERFORM: A Phase II Study of Pemigatinib in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphomas
The purpose of this clinical trial is to learn if the study drug pemigatinib is effective in treating patients with relapsed or refractory B-cell non-Hodgkin lymphomas.
• Subjects aged ≥ 18 years.
• ECOG Performance Status ≤ 2.
• Histologically confirmed MCL or MZL, including EMZL/MALT lymphoma, SMZL, and NMZL.
⁃ -Patients with gastric MALT lymphoma and those who are H. Pylori positive need to have failed a trial of H. Pylori eradication and are either ineligible, have refused, or have failed gastric radiation therapy.
• Have received at least two prior lines of systemic therapy and do not have FDA approved available therapies or have refused them.
• Prior autologous hematopoietic cell transplantation (auto-HCT) and CAR-T cell therapy are eligible.
‣ Patients with prior auto-HCT may be eligible if treatment completed after at least 3 months prior to first treatment
⁃ Patients with CAR T-cell therapy may be eligible if treatment completed after at least 1 month prior to first treatment
• Subject must have an indication for systemic treatment.
• Radiographically measurable disease by computed tomography (CT) scan, defined as at least one lesion \>1.5 cm in size or assessable disease in the opinion of the investigator.
• Life expectancy \>3 months, in the opinion of the investigator.
• Adequate organ function as defined as:
‣ Hematologic:
• Absolute neutrophil count (ANC) ≥ 1000/mm3 (≥1.0 x 10\^9/L) independent of G-CSF support (i.e., no G-CSF within the past 3 days), unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case ANC of 750 cells/mm3 (0.75 x 10\^9/L) is permissible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
∙ Platelet count ≥ 75,000/mm3 (≥75 x 10\^9/L) independent of transfusion support (i.e., no transfusion within the past 3 days) unless there is documented bone marrow involvement in which case platelet count of 50,000 cells/mm3 (0.5 x 10\^9/L) is permissible. Patients must be responsive to transfusion support if given for thrombocytopenia and patients refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
∙ Hemoglobin ≥ 8 g/dL independent of transfusion support (i.e., no transfusion within the past 3 days) unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case hemoglobin of 7 g/dL is permissible. Patients must be responsive to transfusion support if given for anemia and patients refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
⁃ Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN). or \<2.5 x ULN with document liver involvement and/ or Gilbert's disease
∙ AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN ----Subjects with liver involvement will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.
∙ Renal:
⁃ ---Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula.
• For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
‣ Women \< 50 years of age:
∙ --Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
∙ --Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
∙ --Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
⁃ Women ≥ 50 years of age:
• Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
∙ Had radiation-induced menopause with last menses \>1 year ago; or
∙ Had chemotherapy-induced menopause with last menses \>1 year ago; or
∙ Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
• Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.3.1.
• Ability to swallow oral tablets.
• Recovery to baseline or ≤ Grade 2 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator.
• Patients or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial.