# Iomab-ACT: A phase I/II study of 131-I apamistamab targeted lymphodepletion followed by CD19-targeted CAR T-cell therapy for patients with relapsed or refractory B-ALL or DLBCL

> **NIH NIH R42** · ACTINIUM PHARMACEUTICALS, INC. · 2020 · $378,389

## Abstract

ABSTRACT
Despite treatment advances, the prognosis of adult patients with relapsed or refractory (R/R) B-cell acute
lymphoblastic leukemia (B-ALL) and R/R diffuse large B-cell lymphoma (DLBCL) remains poor. Autologous T-
cells modified to express a CD19-targeted chimeric antigen receptor (CAR T-cells) produce durable responses
in subgroups of these patients, which has led to FDA approval of two such therapies to date; numerous other
CAR T-cell therapies are under investigation, including a CD19-targeted CAR T-cell product bearing a CD28
costimulatory domain (19-28z) developed at Memorial Sloan Kettering Cancer Center. However, CAR T-cell
therapy for B-ALL and DLBCL is associated with high risk of severe neurologic toxicity (including
encephalopathy, dysphasia, seizures, and rarely, cerebral edema) and cytokine release syndrome (CRS). Host
monocytes are the major source of elevated cytokines (IL-1, IL-6) observed in the context of neurologic toxicity.
Administration of conditioning or “lymphodepleting” chemotherapy prior to CAR T-cell infusion, most commonly
cyclophosphamide and fludarabine, appears to improve CAR T-cell expansion and efficacy by several
mechanisms. However, a conditioning strategy that depletes monocytes as well as lymphocytes may reduce the
risk of severe neurologic toxicity while preserving antitumor efficacy. The anti-CD45 antibody apamistamab
labeled with 131-iodine (131-I apamistamab) is being investigated as myeloablative conditioning prior to
hematopoietic cell transplantation in the Phase III SIERRA trial for patients with active, R/R acute myeloid
leukemia. In SIERRA, transient lymphodepletion is observed clinically when 131-I apamistamab is given at low
doses for dosimetry. Additionally, in preclinical models, a single low dose of 131-I-radiolabeled anti-CD45
antibody efficiently depletes lymphocytes, myeloid-derived suppressor cells, and regulatory T-cells, without
impact on bone marrow hematopoietic stem cells.
We propose investigating low-dose 131-I apamistamab in lieu of conditioning chemotherapy prior to 19-28z CAR
T-cell therapy in patients with R/R B-ALL or R/R DLBCL, hypothesizing this will more effectively deplete host
monocytes and reduce cerebrospinal fluid (CSF) levels of monocyte-derived cytokines, and thereby lower the
incidence of severe neurologic toxicity following 19-28z CAR T-cell infusion. This clinical trial will be the first to
test radiopharmaceutical conditioning prior to CAR T-cell therapy. The phase I/II study is designed to determine
the maximum tolerated dose of 131-I apamistamab in this setting and subsequently to assess the incidence of
severe neurologic toxicity associated with 131-I apamistamab conditioning and 19-28z CAR T-cell therapy in
patients with R/R B-ALL or R/R DLBCL, as well as antitumor efficacy. A correlative study plan will characterize
the effects of 131-I apamistamab on cytokine profiles in blood and CSF, and on the composition of the immune
cellular microenvironment. Resul...

## Key facts

- **NIH application ID:** 10081925
- **Project number:** 1R42CA254685-01
- **Recipient organization:** ACTINIUM PHARMACEUTICALS, INC.
- **Principal Investigator:** Mark S Berger
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,389
- **Award type:** 1
- **Project period:** 2020-09-09 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10081925

## Citation

> US National Institutes of Health, RePORTER application 10081925, Iomab-ACT: A phase I/II study of 131-I apamistamab targeted lymphodepletion followed by CD19-targeted CAR T-cell therapy for patients with relapsed or refractory B-ALL or DLBCL (1R42CA254685-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10081925. Licensed CC0.

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