Clinical Trials

Inclusion Criteria - Pre-Registration:

• Age ≥ 18 years.
• Confirmed diagnosis of 1 of the following relapsed or refractory B-cell hematologic malignancies: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), large B cell lymphoma (LBCL) including Richter’s transformation from CLL/SLL.
• For CLL/SLL, patients must have received prior therapies, namely a BTK inhibitor or BCL-2 inhibitor. These patients may or may not have received prior antibody directed against CD20. For Follicular Lymphoma, patients must have received prior chemoimmunotherapy including an antibody directed against CD20. For Mantle Cell Lymphoma, patients must have received prior chemoimmunotherapy including an antibody directed against CD20, and a BTK inhibitor. For Marginal Zone Lymphoma, patients must have received prior chemoimmunotherapy including an antibody directed against CD20. For Large B cell Lymphoma, patients must have received prior chemoimmunotherapy including an antibody directed against CD20. Prior exposure to CD19 directed CAR-T cell therapy will be allowed at the discretion of the Principle Investigator. For Richter’s Transformation, patients must have received prior chemoimmunotherapy including an antibody directed against CD20.
• Measurable disease as defined in section:
  • NOTE: To be considered measurable, the must be at least one lesion that has a single diameter of (> 1.5 cm);
  • Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• Prior treatment: Relapsing or progressing patients must have received two or more prior lines of systemic chemoimmunotherapy:
  • NOTE: Prior failed CD19 directed CART cell therapy is allowed.
• Patients must have an ejection fraction (EF) of > 45%.
• Patients must have pulse ox measurements of > 92% on room air 3.2.

Inclusion Criteria - Registration:

• Positive BAFFR test 3.32 Measurable disease as defined in Section 11.0 3.33 ECOG Performance Status (PS) 0, 1 or 2 (Appendix I).
• The following laboratory values obtained ≤ 14 days prior to registration: (See Section 4.0):
  • Hemoglobin ≥ 9.0 g/dL (unless due to documented marrow involvement with disease);
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3 (unless due to documented marrow involvement with disease);
  • Platelet count ≥ 100,000/mm^3 (unless due to documented marrow involvement with disease);
  • Total bilirubin ≤ 1.5 x ULN;
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement);
  • PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy;
  • Patients on a stable, maintenance regimen of anticoagulant therapy for at least 30 days prior to registration may have PT/INR measurements >1.5X ULN if, in the judgment of the investigator, the patient is suitable for the study. • Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula b.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Provide written informed consent understand and comply with protocol-required study procedures.
• Ability to complete questionnaire(s) by themselves or with assistance. 3.38 Willingness to provide mandatory blood specimens for correlative research (see Section 14.0).
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

Exclusion Criteria - Pre-Registration:

• Prior solid organ transplantation.
• Unstable angina, clinically significant arrhythmia, or myocardial infarction ≤ 6 months of prior to pre-registration, or grade 3 or higher pericardial effusion at the time of pre-registration.
• Prior anti-BAFF-R therapies.
• Known contraindication to LD chemotherapy.
• Use of systemic antitumor therapy or investigational agent ≤ 14 days, prior to pre-registration.
• Receiving any other investigational agent which would be considered as a treatment for the BAFF-R.
• Autologous HCT ≤ 60 days prior to pre-registration 3.28 Uncontrolled intercurrent non-cardiac illness including, but not limited to:
  • Previous or concurrent malignancy;
  • Ongoing or active infection;
  • Psychiatric illness/social situations;
  • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy;
  • Persons of childbearing potential who are pregnant or breastfeeding;
  • Life Expectancy of less than 6 weeks;
  • Persons requiring systemic corticosteroids (>10 mg prednisone or equivalent per day) and/or other immunosuppressive therapy. Patients are allowed to use topical corticosteroids;
  • Any other conditions that would limit compliance with study requirements.
• Detectable malignant cells from cerebrospinal fluid (CSF) or magnetic resonance imaging (MRI) indicating brain metastases during screening, or a history of central nervous system (CNS) involvement by malignancy (CSF or imaging) with still active disease. Note: Patients with a history of CNS involvement resolving after treatment and without active disease will be considered eligible if other inclusion criteria are met.
• History of a seizure disorder, major cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Radiation therapy ≤ 14 days prior to pre-registration.
• Prior allogeneic HCT in ≤ 6 months prior to pre-registration; patients with active graft versus host disease (GVHD) will not be eligible regardless of duration from prior allogeneic HCT.
• HIV positive patients are excluded from the study.
• Subjects with NYHA class III or greater heart failure.

Exclusion Criteria - Registration:

• Eligible for auto-HCT based on investigator judgement.
• Presence of active bacterial, viral, or fungal infection that is uncontrolled, based on investigator judgment.
• Patients with active hepatitis B or hepatitis C infections are excluded from the study. Patients who are documented to be HIV positive or proven HIV infection from testing are ineligible for the study. Infectious disease testing (HIV-1, HIV2, HCV antibody and PCR, HBV surface antigen, HBV surface antibody, HBV core antibody) performed ≤ 45 days prior to registration may be considered for subject eligibility.
• Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥5 years prior to registration.
• Persons of childbearing potential who are pregnant or breastfeeding.
• Life expectancy of less than 6 weeks.
• Patients who do not have an ejection fraction (EF) of > 45%.
• Patients who do not have pulse ox measurements of > 92% on room air.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/28/23. Questions regarding updates should be directed to the study team contact.