IOMAB-CAR-T Followed by CAR-T Cell Therapy in R/R DLBCL

NCT06768905 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STU-2024-1091; SCCC-03424
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to determine the safety, efficacy and tolerability of a single 50 mCi dose of 131I-Apamistamab given prior to FDA approved (commercially available) infusion in patients with Relapsed or refractory (R/R) non-Hodgkin lymphoma.

Conditions

Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (safety) -Part A (safety run-in)

  The number and percentage of patients with DLTs will be summarized for Part A using the DLT Analysis Set. The data analysis set will include all patients in Part A who received study medication and either experienced a DLT or completed at least 75% of the DLT period. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.

  Start of treatment up to 30 days post CAR T-cell infusion

• Complete response (efficacy) -Part B (Cohort expansion)

  Measurement of effect (response and progression) will be conducted using a PET/CT scan which will report the Lugano criteria for response at screening 1 and 2 (if PET available), Day 30 +7 days, and Day 100 +/-7 days

  Screening visit to Day 100 visit

Secondary Outcomes (2)

• Severity of cytokine release syndrome (CRS)

  within 100 days of CAR T-cell infusion

• Severity of immune effector cell-associated neurotoxicity (ICANS)

  within 100 days of CAR T-cell infusion

Study Arms (2)

Part A (Safety run-in)

EXPERIMENTAL

131I-Apamistamab dose will be given 5-7 days prior to a single infusion of CD-19 CAR-T cell therapy

Drug: Iomab-B; Drug: CAR-T cell

Part B (cohort expansion)

EXPERIMENTAL

131I-Apamistamab dose will be given 5-7 days prior to a single infusion of CAR-T cell therapy

Drug: Iomab-B; Drug: CAR-T cell

Interventions

CAR-T cell DRUG

CAR-T cell therapy

Also known as: CAR-T cell therapy

Part A (Safety run-in); Part B (cohort expansion)

Iomab-B DRUG

single 50 mCi dose of 131I-Apamistamab given prior to CAR-T cell infusion.

Also known as: Iomab-ACT, 131I-Apamistamab

Part A (Safety run-in); Part B (cohort expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with diffuse large B-cell lymphoma (de novo or DLBCL transformed from an indolent lymphoma (follicular lymphoma, chronic lymphocytic leukemia \[Richter syndrome\]) or high-grade B-cell lymphoma (HGBL): ("DLBCL patients")
• Defined as relapsed or refractory DLBCL or high-grade B-cell lymphoma (HGBL) following at least one or more prior chemoimmunotherapy regimen (with at least one course including an anthracycline and CD20-directed therapy) following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and requiring further treatment and deemed to be candidates for standard of care CAR-T therapy. This includes patients with primary refractory disease (failure to achieve complete response (CR) to first-line therapy), relapsed disease within 12 months of first line chemoimmunotherapy or relapsed/refractory disease after 2 or more prior lines of systemic therapy.
• Relapsed or refractory disease must be confirmed with a repeat biopsy within the last 12 months.
• Age ≥ 18 years of age
• Creatinine clearance ≥50 mL/min as calculated by the Cockroft-Gault formula.
• Total bilirubin ≤1.5x upper limit of normal , AST and ALT ≤3x upper limit of normal (ULN), unless liver dysfunction is thought to be related to underlying malignancy or secondary to Gilbert's disease in which case the direct bilirubin should be ≤3.0 mg/dL, and AST and ALT ≤5x ULN.
• Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air or per institutional guidelines.
• Thyroid function tests (TSH, FT4) ≤2x upper limit of normal (ULN)
• Adequate bone marrow function meeting the following criteria as defined below, without requiring blood product or granulocyte-colony stimulating factor support in the 7 days prior to screening and start of 131I-Apamistamab treatment.
• Absolute neutrophil count ≥1.0k/µL,
• Platelets ≥50k/µL,
• Hemoglobin ≥8g/dL.
• Performance status: ECOG performance status 0-2.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, and/or abstinence) prior to study entry, and for the duration of study treatment, and for 30 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

You may not qualify if:

• Pregnant or lactating patients.
• Impaired cardiac function (LVEF \<40%) as assessed by echocardiogram or MUGA scan.
• Patients with active graft versus host disease following allogeneic hematopoietic cell transplantation requiring systemic T-cell suppressive therapy are ineligible.
• Patients with active autoimmune disease requiring systemic T-cell suppressive therapy are ineligible.
• Patients with the following cardiac conditions will be excluded:
• New York Heart Association (NYHA) stage III or IV congestive heart failure
• Myocardial infarction ≤6 months prior to enrollment
• Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
• Have current or prior positive test results for human immunodeficiency virus (HIV) or hepatitis B (HBV) or C (HCV), with the following exceptions:
• Patients who have positive HBV test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HbsAg), negative anti- hepatitis B core protein (HBc) and positive antibody to the HbsAg (anti-HBs) are not excluded.
• Patients who have antibodies to HCV or who have hepatitis B core antibody, with undetectable viremia by PCR, and with adequate organ function as defined in the protocol, are not excluded.
• Patients with uncontrolled systemic fungal, bacterial, viral, or other infections are ineligible.
• Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin.
• Patients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible.
• Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Actinium Pharmaceuticals: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Farrukh Awan, MD, MS, MBA

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Farrukh Awan, MD, MS, MBA

CONTACT

817-676-9670; farrukh.awan@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Internal Medicine

Study Record Dates

• First Submitted: January 6, 2025
• First Posted: January 10, 2025
• Study Start: April 25, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: April 16, 2026

Record last verified: 2025-04

Locations

US (1)