# Project 6: Clinical Trials Focusing on Microbiota and Novel Cell Therapies

> **NIH NIH P01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $393,942

## Abstract

Project Abstract
 Allogeneic hematopoietic cell transplantation (allo-HCT) is an established curative strategy for a variety of
malignant and non malignant hematologic disorders. Although significant advances have been made; 30-50%
of patients will still die from either relapse, infections or complications of graft versus host disease. The primary
objective of Project 6 is to conduct a series of clinical trials (CTs) testing novel approaches that address major
challenges to the success of alloHCT. The CTs included in this project address one of two specific aims. SA1
will test and develop novel cellular approaches to prevent relapse or enhance immune reconstitution post
alloHCT. This aim will be addressed by two CTs. CT1 is “A randomized, phase 2 study of donor allograft
CD34+ selection versus TCR-αβ+ cell depletion GVHD prophylaxis for patients undergoing allogeneic
hematopoietic cell transplantation for high risk hematologic malignancies” in which we will compare immune
reconstitution between a novel graft manipulation strategy that depletes only alpha/beta T cells and our well
established CD34 selection procedure. The goal of this study is to demonstrate that the novel graft
manipulation strategy will result in a more robust immune reconstitution with reduction in the risk of infections
and improved HCT outcomes. CT2 is a Phase I Trial Using In Vitro Expanded Allogeneic Epstein-Barr Virus
Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19 Antigen in B-cell
Malignancies. SA2 will ascertain the impact of gastrointestinal (GI) microbiota on HCT outcomes. This aim will
be addressed through the performance of two CTs. CT3 addresses microbiome preservation through rationale
antibiotic use (Open-label phase II randomized trial of empiric treatment of fever and neutropenia (F&N) with
piperacillin-tazobactam vs. cefepime in recipients of unmodified allogeneic HCT). CT4 will test the ability of 3rd
party fecal microbiota transplants to restore microbiota diversity (Phase II Trial of 3rd Party Fecal Microbiota
Transplantation (FMT) in Recipients of Allogeneic HCT).
 More than 9000 allo-HCTs will be performed in the United States this year. The two SAs with the six
proposed clinical trials in this project address the most common causes of treatment failure. The three trials
exploring the impact of the GI microbiome on HCT outcomes will either devise new strategies to prevent or
remediate loss of GI microbiome diversity while at the same time increasing our understanding of the
mechanisms by which bacteria or their products can cause or prevent harm after an allo-HCT. The three
clinical trials proposed will test novel cellular strategies to address relapse and immune reconstitution. These
strategies will allow us to develop less toxic and more effective allo-HCT regimens in the future.

## Key facts

- **NIH application ID:** 9984299
- **Project number:** 5P01CA023766-40
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Sergio A Giralt
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,942
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984299

## Citation

> US National Institutes of Health, RePORTER application 9984299, Project 6: Clinical Trials Focusing on Microbiota and Novel Cell Therapies (5P01CA023766-40). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984299. Licensed CC0.

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