HEME-25: Open-Label Feasibility Study of Elranatamab Utilized in Newly Diagnosed Plasmablastic Lymphoma With or Without HIV (HEME-25)

HEME-25: Open-Label Feasibility Study of Elranatamab Utilized in Newly Diagnosed Plasmablastic Lymphoma With or Without HIV in Consolidation After Definitive Therapy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Plasmablastic Lymphoma; Hiv; Consolidation
• Intervention / Treatment: Drug: Elranatamab (Elra)

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).

• Study Type: Interventional
• Enrollment (Estimated): 17
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Paul Rubinstein, MD; Phone Number: 312 413 1300; Email: paulgr@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria:

• Prior BCMA bispecific therapy
• Stable or progressive disease following front-line therapy as determined by the investigator
• Receiving any other investigational agents
• Expected survival < 2 months
• Known or suspected PBL involvement of the parenchymal brain or spinal cord at diagnosis. Asymptomatic leptomeningeal disease only will be allowed.
• Uncontrolled intercurrent illness, including but not limited to uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Concurrent malignancy requiring active therapy within the last 3 years, except for the following:

  • Basal cell carcinoma limited to the skin
  • Squamous cell carcinoma limited to the skin
  • Carcinoma in situ of the cervix or breast
  • Adequately treated lentigo malignant melanoma
  • Localized prostate cancer
  • Active therapy consists of adjuvant or maintenance therapy to reduce the risk of recurrence of a malignancy that was previously treated with curative intent and with no evidence of active disease within 2 years prior to screening
• Pregnant or nursing
• PWH with a history of AIDS-defining opportunistic infection within the past year
• Receipt of a live vaccine within 28 days prior to the first dose of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single-arm Open label study of Elra of pts with PBL; 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).

Drug: Elranatamab (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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Elra consolidation therapy	Evaluation of completion of (Elra) consolidation following definitive therapy in patients with PBL, defined as the proportion of patients completing at least 3 cycles	12 weeks ( 3 cycles)
Estimate the complete response in HIV+/ HIV- patients	Estimate the complete response (CR) rate (per 2014 LUGANO criteria)Ref . in HIV-positive and HIV-negative patients after 6 months of consolidation.	6 months
Evaluate the safety and tolerability of Elra consolidation	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess event-free survival, progression-free and overall survival of Elra	Assess event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) at 1- and 2-year post-completion of Elra consolidation	1 year and 2 year
Estimate the conversion rate	Estimate the conversion rate from pre-consolidation partial response (PR) to CR at the end of Cycle 3 and Cycle 6.	Cycle 3 and cycle 6 (12 weeks and 24 weeks)
Evaluate quality of life (QoL) outcomes as measured by changes from baseline	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.	6 months
Assess the effects of Elra on CD4 T-cell counts	Assess the effects of Elra on CD4 T-cell counts and HIV-1 viral load in people with HIV (PWH).	6 months

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Neoplasms; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Neoplasms by Histologic Type; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Slow Virus Diseases; Lymphoma, B-Cell; Lymphoma; HIV Infections; Lymphoma, Large B-Cell, Diffuse; Hemic and Lymphatic Diseases; Plasmablastic Lymphoma; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 2025-1210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No