Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies (PDX+Romi)

November 18, 2022 updated by: Jennifer Amengual

Phase I/IIA Study of the Novel Antifolate Agent Pralatrexate in Combination With the Histone Deacetylase Inhibitor Romidepsin for the Treatment of Patients With Peripheral T-cell Lymphoma

This is a study to test how safe the combination of the drugs Romidepsin and Pralatrexate are in patients with lymphoid malignancies and to determine the dose of the combination of drugs that is safest. If the combination is determined to be safe, the study will continue accrual patients with peripheral T-Cell lymphoma (PTCL).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The non- Hodgkin lymphomas (NHL) represent a heterogeneous group of malignancies. Under the rubric of lymphoma exist some of the fastest growing cancers known to science, (Burkett's lymphoma, lymphoblastic lymphoma/leukemia), as well as some of the most indolent (small lymphocytic lymphoma, follicular lymphoma, and marginal zone lymphoma). This remarkable diversity of biology imposes significant challenges. Researchers are seeking to understand the cell of origin and differentiate what are sometimes subtle differences between the related sub-types of disease; and to identify the best treatments for these subtypes, with the ever-increasing likelihood that new understanding of the molecular pathogenesis of these diseases will result in an increase in new drugs for specific target populations.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • New York
      • New York, New York, United States, 10019
        • Columbia University Irving Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Phase I: Patients must have histologically confirmed relapsed or refractory Non-Hodgkin's lymphoma, Hodgkin's Disease or multiple myeloma (defined by World Health Organization (WHO) criteria).

Phase II: Patients must have histologically confirmed relapsed or refractory T-Cell Lymphoma (as defined by WHO criteria).

  • Must have received first line chemotherapy. No upper limit for the number of prior therapies
  • Evaluable Disease
  • Age ≥18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Patients must have adequate organ and marrow function as defined in the protocol
  • Adequate Contraception
  • Ability to understand and the willingness to sign a written informed consent document
  • Inclusion Criteria for Multiple Myeloma patients specified in the protocol

Exclusion Criteria:

  • Prior Therapy

    • Exposure to chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
    • Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs
    • No other investigational agents are allowed
  • Central nervous system metastases, including lymphomatous meningitis
  • History of allergic reactions to Pralatrexate or Romidepsin
  • Uncontrolled intercurrent illness
  • Pregnant women
  • Nursing women
  • Current malignancy or history of a prior malignancy, as outlined in the protocol
  • Patient known to be Human Immunodeficiency Virus (HIV)-positive
  • Active Hepatitis A, Hepatitis B, or Hepatitis C infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Phase I: Schedule A
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle
Drug: Pralatrexate

Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2

Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.

Other Names:
  • Folotyn
Drug: Romidepsin

Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.

Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.

Other Names:
  • Istodax
EXPERIMENTAL: Phase I: Schedule B
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle
Drug: Pralatrexate

Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2

Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.

Other Names:
  • Folotyn
Drug: Romidepsin

Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.

Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.

Other Names:
  • Istodax
EXPERIMENTAL: Phase II
Subjects will receive Pralatrexate 25 mg/m2 and Romidepsin 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle
Drug: Pralatrexate

Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2

Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.

Other Names:
  • Folotyn
Drug: Romidepsin

Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.

Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.

Other Names:
  • Istodax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin
Time Frame: Up to 1.5 years
For Phase I
Up to 1.5 years
Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma
Time Frame: Up to 3 years
For Phase II
Up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum number of cycles received
Time Frame: Up to 1.5 years
For Phase II
Up to 1.5 years
Number of dose delays at the MTD
Time Frame: Up to 1.5 years
For Phase I
Up to 1.5 years
Overall response rate (ORR) of the study population
Time Frame: Up to 1.5 years
For Phase I
Up to 1.5 years
Duration of response (DOR) of the combination in patients with T-Cell Lymphoma
Time Frame: Up to 3 years
For Phase II
Up to 3 years
Overall survival (OS) of patients with T-Cell Lymphoma on study
Time Frame: Up to 3 years
For Phase II
Up to 3 years
Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma
Time Frame: Up to 3 years
For Phase II
Up to 3 years
Number of dose reductions at the MTD
Time Frame: Up to 1.5 years
For Phase I
Up to 1.5 years
Progression free survival (PFS) of the study population
Time Frame: Up to 1.5 years
For Phase I
Up to 1.5 years
Duration of response (DOR) of the study population.
Time Frame: Up to 1.5 years
For Phase I
Up to 1.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jennifer Amengual

Investigators

  • Principal Investigator: Jennifer Amengual, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 9, 2013

Primary Completion (ACTUAL)

September 1, 2022

Study Completion (ACTUAL)

September 1, 2022

Study Registration Dates

First Submitted

September 9, 2013

First Submitted That Met QC Criteria

September 17, 2013

First Posted (ESTIMATE)

September 20, 2013

Study Record Updates

Last Update Posted (ACTUAL)

November 23, 2022

Last Update Submitted That Met QC Criteria

November 18, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAJ5656

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on Pralatrexate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Benin

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe