# A Randomized, Phase IIB, Multicenter, Trial of Oral Azacytidine Plus Romidepsin versus Investigator's Choice in Patients with Relapse or Refractory Periperal T-cell lymphoma (PTCL).

> **NIH FDA R01** · UNIVERSITY OF VIRGINIA · 2020 · $807,732

## Abstract

Project Abstract
CHOP-based regimens, the present standard of care for peripheral T-cell lymphoma (PTCL), were established
in aggressive B-cell malignancies and extrapolated to the PTCL. As a result, the median survival of patients with
PTCL is only 1 to 3 years, with a median 5-year survival of only 20-25%. Major challenges to develop PTCL-
specific treatment relate to their rarity and heterogeneity. Specifically, the annual incident rate ratio of all PTCLs
is 1.3673 per 100,000 among all races on average and their prevalence rate is 5.30 per 100,000. The extreme
heterogeneity is affirmed by the fact that the WHO recognizes 30 distinct subtypes of the disease. Many lines of
data now suggest that the PTCL exhibit a unique vulnerability to epigenetic modifiers. In order to identify
potentially new standards for the disease, we will conduct a randomized, phase IIB, multicenter trial of Oral
Azacytidine (AZA) plus Romidepsin (ROMI) versus Investigator’s Choice (IC) including romidepsin, belinostat,
pralatrexate and gemcitabine in patients with Relapse or Refractory (R/R) PTCL. We anticipate generating
sufficient data that will inform a ‘go-no-go’ decision regarding a full scale randomized Phase 3. To date, several
agents have gained FDA accelerated approval for the treatment of R/R PTCL. Based on these examples, the
logic for a potential regulatory study design is as follows: the patient population is “patients with PTCL who have
received one prior systemic therapy.” This patient population was studied in all precedent examples of
accelerated approvals (pralatrexate, romidepsin, belinostat). While the term PTCL encompasses multiple T-cell
lymphoma histology’s, the FDA has permitted registration trials to be conducted in this category of T-cell
lymphoma malignancies due to the rarity of the disease. We will adopt the traditional endpoint of progression
free survival (PFS), used for regular approvals of new agents in R/R lymphomas (B- and T-lymphomas), in
contrast to response rate or CR rate used for accelerated approvals. Lastly, the control arm is an investigator
choice that includes appropriate and clinically meaningful drugs for this trial. Finally, the correlative samples
obtained from patients on trial will determine how the genetic features of the disease influence clinical outcome
and will clarify the immunologic effects induced by the combination. We believe this study will transform how we
think about future treatment paradigms, and improve the outcomes of patients with PTCL.

## Key facts

- **NIH application ID:** 9965629
- **Project number:** 1R01FD006814-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Enrica Marchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $807,732
- **Award type:** 1
- **Project period:** 2020-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965629

## Citation

> US National Institutes of Health, RePORTER application 9965629, A Randomized, Phase IIB, Multicenter, Trial of Oral Azacytidine Plus Romidepsin versus Investigator's Choice in Patients with Relapse or Refractory Periperal T-cell lymphoma (PTCL). (1R01FD006814-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965629. Licensed CC0.

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