Consolidation, Hiv, Plasmablastic Lymphoma
Conditions
Brief summary
This is a single-arm feasibility trial in which patients with histologically confirmed plasmablastic lymphoma (PBL) with or without HIV, who have achieved a Complete Response or Partial Response after definitive frontline chemotherapy, will receive Elranatamab (Elra) consolidation.
Detailed description
Patients will receive Elra subcutaneously for up to six 28-day cycles, beginning with a step-up dosing schedule (12 mg on day 1, 32 mg on day 4, followed by 76 mg weekly on days 8, 15, and 22 of Cycle 1). Patients will transition to 76 mg every 2 weeks (days 1 and 15) during Cycles 2 and 3, followed by an interim PET/CT assessment at the end of Cycle 3. During cycles 4 through 6, all patients will receive 76 mg every 4 weeks (on day 1 of each cycle). Participants will undergo disease assessment with PET/CT at the end of Cycle 3, post-end of treatment (EOT) visit, and every 6 months thereafter (±2 weeks) for up to 2 years to assess recurrence and survival. Routine clinical follow-up will continue every 3 months, as per the standard of care (SOC).
Interventions
DRUGElranatamab (Elra)
Elra will be administered subcutaneously on day 1, day 4, then weekly on day 8, 15 and day 22 completing 1 cycle. Up to 6 cycles may be given.
Sponsors
University of Illinois at Chicago
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Elra subcutaneously for up to six 28-day cycles, beginning with a step-up dosing schedule (12 mg on day 1, 32 mg on day 4, followed by 76 mg weekly on days 8, 15, and 22 of Cycle 1).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years at time of consent * ECOG performance status (PS) 0 or 1 * Histologically and immunophenotypically confirmed PBL * Ann Arbor stage at initial diagnosis: stage I with lactate dehydrogenase (LDH) \> upper limit of normal (ULN) and/or bulky disease \>7.5 cm or stage II-IV * Received definitive front-line therapy for PBL with end-of-treatment PR or CR * Adequate bone marrow function with recovery from prior therapy, defined as: * ANC ≥ 500 cells/mcL * Platelet count ≥ 50,000 cells/mcL * Availability of archival tumor tissue (block or unstained slides) for mandatory central pathology review and correlative BCMA testing. Central pathology review and BCMA testing may be completed after enrollment. * Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization. If a subject is unable to consent, a LAR may provide consent on their behalf. * As determined at the discretion of the enrolling physician or protocol designee, the ability of the subject to understand and comply with study procedures for the entire length of the study * If capable of becoming pregnant: Negative serum or urine pregnancy test * If HIV-positive: * Receiving effective combined antiretroviral therapy * CD4+ T-cell count ≥ 50 cells/mcL within 4 weeks before enrollment
Exclusion criteria
Key inclusion criteria: * Age ≥ 18 years at time of consent * ECOG performance status (PS) 0 or 1 * Histologically and immunophenotypically confirmed PBL * Ann Arbor stage at initial diagnosis: stage I with lactate dehydrogenase (LDH) \> upper limit of normal (ULN) and/or bulky disease \>7.5 cm or stage II-IV * Received definitive front-line therapy for PBL with end-of-treatment PR or CR * Adequate bone marrow function with recovery from prior therapy, defined as: * ANC ≥ 500 cells/mcL * Platelet count ≥ 50,000 cells/mcL * Availability of archival tumor tissue (block or unstained slides) for mandatory central pathology review and correlative BCMA testing. Central pathology review and BCMA testing may be completed after enrollment. * Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization. If a subject is unable to consent, a LAR may provide consent on their behalf. * As determined at the discretion of the enrolling physician or protocol designee, the ability of the subject to understand and comply with study procedures for the entire length of the study * If capable of becoming pregnant: Negative serum or urine pregnancy test * If HIV-positive: * Receiving effective combined antiretroviral therapy * CD4+ T-cell count ≥ 50 cells/mcL within 4 weeks before enrollment Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Elra consolidation therapy | 12 weeks ( 3 cycles) | Evaluation of completion of (Elra) consolidation following definitive therapy in patients with PBL, defined as the proportion of patients completing at least 3 cycles |
| Estimate the complete response in HIV+/ HIV- patients | 6 months | Estimate the complete response (CR) rate (per 2014 LUGANO criteria)Ref . in HIV-positive and HIV-negative patients after 6 months of consolidation. |
| Evaluate the safety and tolerability of Elra consolidation | 6 months | To evaluate the safety and tolerability of Elra consolidation, including the incidence, severity, and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), assessed by ASTCT consensus criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess event-free survival, progression-free and overall survival of Elra | 1 year and 2 year | Assess event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) at 1- and 2-year post-completion of Elra consolidation |
| Estimate the conversion rate | Cycle 3 and cycle 6 (12 weeks and 24 weeks) | Estimate the conversion rate from pre-consolidation partial response (PR) to CR at the end of Cycle 3 and Cycle 6. |
| Evaluate quality of life (QoL) outcomes as measured by changes from baseline | 6 months | Evaluate quality of life (QoL) outcomes as measured by changes from baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - High-Grade Non-Hodgkin Lymphoma 29 items (EORTC QLQ-NHL-HG29) scores. |
| Assess the effects of Elra on CD4 T-cell counts | 6 months | Assess the effects of Elra on CD4 T-cell counts and HIV-1 viral load in people with HIV (PWH). |
Contacts
CONTACTPaul Rubinstein, MD
Outcome results
None listed