Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies
B-cell Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
About this trial
This is an interventional treatment trial for B-cell Non-Hodgkins Lymphoma focused on measuring NHL, B-cell Prolymphocytic Leukemia, Transformed Lymphoma, Burkitt's Lymphoma, Mantle Cell Lymphoma, Hairy Cell Leukemia, Splenic Marginal Zone Lymphoma, Waldenstrom's Macroglobulinemia, Variant Hairy Cell Leukemia, Splenic B-cell Lymphoma/Leukemia, Lymphoplasmacytic Lymphoma, Extranodal Marginal Zone Lymphoma (MALT), MALT Lymphoma, Nodal Marginal Zone Lymphoma, Follicular Lymphoma, In Situ Follicular Neoplasia, Duodenal-type Follicular Lymphoma, Large B-cell Lymphoma with IRF4 rearrangement, Primary Cutaneous Follicle Center Lymphoma, Diffuse Large B-cell Lymphoma, DLBCL, T-cell/Histiocyte-Rich Large B-cell Lymphoma, Primary Cutaneous DLBCL, leg type, EBV-positive DLBCL, NOS, EBV-positive Mucocutaneous Ulcer, DLBCL Associated with Chronic Inflammation, Lymphomatoid Granulomatosis, Primary Mediastinal (Thymic) Large B-cell Lymphoma, Intravascular Large B-cell Lymphoma, ALK+ Large B-cell Lymphoma, Plasmablastic Lymphoma, Primary Effusion Lymphoma, HHV8+ DLBCL, Burkitt-like Lymphoma with 11q Aberration, High-grade B-cell Lymphoma, B-cell Lymphoma, unclassifiable, Post-transplant Lymphoproliferative Disorder, PTLD, SLL, High-grade Lymphoma, Richter's Transformation
Eligibility Criteria
Inclusion Criteria:
- Able to provide written informed consent
- Diagnosis of either Non-CLL B cell malignancy or CLL/SLL
- Ineligible for or have exhausted standard therapeutic options and have relapsed or refractory disease
- ECOG performance status 0-2
- Fertile patients must agree to use highly effective contraception during and for 5 months (male patients) and 8 months (female patients) after last dose of XmAb13676
- Able and willing to complete the entire study
Additional Patient Inclusion Criteria for the DLBCL Cohort (Expansion Phase)
- Histologically confirmed diagnosis (specified by 2016 World Health Organization) of DLBCL or transformed low-grade lymphoma with measurable disease
- Patient must be refractory or have relapsed after 2 or more standard therapeutic options, at least one of which must have included anti-CD20 antibody therapy.
- Not a candidate for or refusing treatment with hematopoietic stem cell transplantation
Additional Patient Inclusion Criteria for the Follicular Lymphoma Cohort (Expansion Phase)
- Diagnosis of follicular lymphoma Grades 1-3a
- Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens.
Exclusion Criteria:
- Cytotoxic chemotherapy, radiotherapy, or immunotherapy including other anti-CD20 antibodies within 4 weeks, or small molecule or investigational agents within 6 elimination half-lives of the first dose of XmAb13676
- Prior allogeneic stem cell or solid organ transplantation
- Failure to recover from Grade 3 or 4 toxicity from previous treatment
- Multiple myeloma/plasma cell leukemia or B cell acute lymphoblastic leukemia
- Known intolerance to CD20 monoclonal antibody therapy
- History of primary central nervous system lymphoma or neoplastic central nervous system disease
- Platelet count < 50 x 10^9/L
- Absolute neutrophil count < 1.0 x 10^9/L
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at screening > 3x upper limit of normal (ULN)
- Bilirubin > 1.5 mg/dL unless prior diagnosis and documentation of ongoing hemolysis or Gilbert's syndrome has been made)
- Estimated creatinine clearance < 50 40 mL/min
- Active/uncontrolled autoimmune disease
- Clinically significant cardiac/cardiovascular disease, or pulmonary compromise
- Seizure disorder
- History of stroke with the past year6 mos prior to study entry
- History or evidence of a clinically unstable/uncontrollable disorder, condition or disease other than primary malignancy, that in the opinion of the Investigator would pose a risk to the patient safety or interfere with the study evaluation, procedures or completion
- Evidence of any serious bacterial, viral, parasitic or systemic fungal infections within the 30 days prior to study entry
- Positive test for human immunodeficiency virus (HIV) or hepatitis C (HCV) antibodies (unless HCV viral load test by PCR is negative)
- Positive test for HbsAg, or positive test for HBcAb (unless serology is positive due to recent intravenous immunoglobulin therapy). HBcAb positivity will be allowed if HBsAb is present.
- Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, and 8 months after the last dose of study drug
- Positive urine pregnancy test (ie, urine human chorionic gonadotropin) at screening
- Live viral vaccine within 2 weeks of the first dose of XmAb13676
Sites / Locations
- Moores UC San Diego Cancer Center
- Mayo Clinic
- Northside HospitalRecruiting
- Northwestern University
- The University of Chicago MedicineRecruiting
- University of MichiganRecruiting
- Roswell Park Cancer Center
- Gabrail Cancer Center Research
- The Ohio State University Wexner Medical Center and James Cancer HospitalRecruiting
- MD Anderson Cancer CenterRecruiting
- UVA Health System, Division of Hematology & Oncology
- Swedish Cancer InstituteRecruiting
- Froedtert Hospital and Medical College of WisconsinRecruiting
- Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud OuestRecruiting
- Hopital Henri MondorRecruiting
- Institut Paoli Calmette Dpt of Oncology/HematologyRecruiting
- Chu Montpellier, Hematologie Clinique St. EloiRecruiting
- CHU de NantesRecruiting
- Centre Antoine LacassagneRecruiting
- CHU Haut-Leveque, Service d'Hematologie Clinique et Therapie CellulaireRecruiting
- Centre Hospitalier Lyon-Sud, Service d'HematologieRecruiting
- Centre Henri BecquerelRecruiting
- Institut Universitaire du Cancer Toulouse OncopoleRecruiting
- CLCC Institut Gustave RoussyRecruiting
- Inje University Busan Paik HospitalRecruiting
- Dong A University Medical Center (Dong A University Hospital)Recruiting
- Gachon University Gil Medical CenterRecruiting
- Seoul National University College of Medicine, Seoul National University Bungdang HospitalRecruiting
- Seoul National University HospitalRecruiting
- Samsung Medical CenterRecruiting
- The Catholic University of Korea, Seoul St. Mary's HospitalRecruiting
- Ewha Womans University Mokdong HospitalRecruiting
- Royal Marsden Hospital (RMH) - Royal Marsden NHS Foundation TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Non-CLL B Cell Malignancies (Group NHL) Part A
CLL/SLL (Group CLL) Part A
Non-CLL B Cell Malignancies (Group NHL) Part B
CLL/SLL (Group CLL) Part B
Non-CLL B Cell Malignancies (Group NHL) Part C / Expansion
Non-CLL B Cell Malignancies (Group NHL) Part D / Expansion
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
XmAb13676 administered SC up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion