# BMT Core- Medical College of Wisconsin

> **NIH NIH UG1** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $234,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The Medical College of Wisconsin (MCW) hematopoietic cell transplant (HCT) and cellular therapy program
proposes to continue its contributions as a BMT CTN Core Center with its expertise in HCT, novel cell and gene
therapies, and continued stellar accrual to BMT CTN trials along with high-quality data submission. We also
propose a trial addressing a high-priority concept identified at the 2021 BMT CTN State of the Science
Symposium (SOSS) that builds on MCW’s experience in developing a first-in-human bispecific chimeric antigen
receptor (CAR T) cell product targeting two B cell antigens, CD19 and CD20 (CAR20.19). Results of a Phase 1
dose-escalation study published in Nature Medicine in 2020 identified a safe dose for Phase II studies while
providing preliminary efficacy and safety data in patients with B-cell malignancies. This led to the development
of a Phase I/II single-center study at MCW for relapsed, refractory (R/R) mantle cell lymphoma (MCL)
(NCT04186520). Despite advances in therapies for MCL that have improved progression-free survival (PFS),
patients with adverse features, including TP53 mutation, 17p deletions, complex karyotype, and blastoid
histology, continue to have poor outcomes and survival. As MCL is known to have both CD19 and CD20
expression, we hypothesized that dual targeting with CAR20.19 T cells could improve PFS and overall survival
in R/R MCL compared to currently available therapies. We can now report promising results in 17 patients with
an overall response rate of 100% and only two patients relapsing to date with a median follow-up of 1 year for
all patients. Excitingly, these responses occurred in the setting of limited CAR-associated toxicity with no patients
with grade 3-4 cytokine release syndrome. We now propose a Phase II multicenter study of MB-CART2019.1
(zamtocabtagene autoleucel) therapy as frontline consolidation for high-risk Mantle Cell Lymphoma. As
identified in the SOSS report in 2021, improving outcomes with novel cell-based therapies for high-risk
MCL is an unmet clinical need. Given our preliminary single center data with excellent efficacy, a favorable
toxicity profile, and our in-depth experience with this product (>90 patients with B-cell non-Hodgkin lymphoma
treated with CAR20.19 T cells since 2017), we are uniquely poised to develop and lead this trial within the BMT
CTN. As high-risk MCL represents a small subset of patients in a disease that only represents 5% of all newly
diagnosed lymphomas, the BMT CTN is the optimal organization to successfully conduct the proposed cell
therapy trial. We hypothesize that dual-targeted CAR20.19 T-cell therapy will improve outcomes for high-risk
MCL patients compared to historical outcomes and represent an important innovation in the field to redefine the
treatment approaches for patients with adverse prognostic MCL.

## Key facts

- **NIH application ID:** 10937661
- **Project number:** 2UG1HL138641-08
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Nirav Shah
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,000
- **Award type:** 2
- **Project period:** 2017-07-27 → 2031-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937661

## Citation

> US National Institutes of Health, RePORTER application 10937661, BMT Core- Medical College of Wisconsin (2UG1HL138641-08). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10937661. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*