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

Primary Purpose

Lymphoid Malignancies, Multiple Myeloma, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pralatrexate
Romidepsin
Sponsored by
Jennifer Amengual
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoid Malignancies focused on measuring Lymphoid Malignancies, Multiple Myeloma, Lymphoma, Hodgkin Lymphoma, Non-hodgkin Lymphoma, Follicular Lymphoma, Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Burkitt Lymphoma, Waldenstrom Macroglobulinemia, Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Beth Israel Deaconess Medical Center
  • Columbia University Irving Medical Center
  • Fox Chase Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase I: Schedule A

Phase I: Schedule B

Phase II

Arm Description

Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle

Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin
For Phase I
Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma
For Phase II

Secondary Outcome Measures

Maximum number of cycles received
For Phase II
Number of dose delays at the MTD
For Phase I
Overall response rate (ORR) of the study population
For Phase I
Duration of response (DOR) of the combination in patients with T-Cell Lymphoma
For Phase II
Overall survival (OS) of patients with T-Cell Lymphoma on study
For Phase II
Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma
For Phase II
Number of dose reductions at the MTD
For Phase I
Progression free survival (PFS) of the study population
For Phase I
Duration of response (DOR) of the study population.
For Phase I

Full Information

First Posted
September 9, 2013
Last Updated
November 18, 2022
Sponsor
Jennifer Amengual
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1. Study Identification

Unique Protocol Identification Number
NCT01947140
Brief Title
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
Acronym
PDX+Romi
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 9, 2013 (Actual)
Primary Completion Date
September 1, 2022 (Actual)
Study Completion Date
September 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jennifer Amengual

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoid Malignancies, Multiple Myeloma, Lymphoma, Hodgkin Lymphoma, Non-hodgkin Lymphoma
Keywords
Lymphoid Malignancies, Multiple Myeloma, Lymphoma, Hodgkin Lymphoma, Non-hodgkin Lymphoma, Follicular Lymphoma, Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Burkitt Lymphoma, Waldenstrom Macroglobulinemia, Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase I: Schedule A
Arm Type
Experimental
Arm Description
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle
Arm Title
Phase I: Schedule B
Arm Type
Experimental
Arm Description
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle
Arm Title
Phase II
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Pralatrexate
Other Intervention Name(s)
Folotyn
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Romidepsin
Other Intervention Name(s)
Istodax
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin
Description
For Phase I
Time Frame
Up to 1.5 years
Title
Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma
Description
For Phase II
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Maximum number of cycles received
Description
For Phase II
Time Frame
Up to 1.5 years
Title
Number of dose delays at the MTD
Description
For Phase I
Time Frame
Up to 1.5 years
Title
Overall response rate (ORR) of the study population
Description
For Phase I
Time Frame
Up to 1.5 years
Title
Duration of response (DOR) of the combination in patients with T-Cell Lymphoma
Description
For Phase II
Time Frame
Up to 3 years
Title
Overall survival (OS) of patients with T-Cell Lymphoma on study
Description
For Phase II
Time Frame
Up to 3 years
Title
Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma
Description
For Phase II
Time Frame
Up to 3 years
Title
Number of dose reductions at the MTD
Description
For Phase I
Time Frame
Up to 1.5 years
Title
Progression free survival (PFS) of the study population
Description
For Phase I
Time Frame
Up to 1.5 years
Title
Duration of response (DOR) of the study population.
Description
For Phase I
Time Frame
Up to 1.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Amengual, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29141948
Citation
Amengual JE, Lichtenstein R, Lue J, Sawas A, Deng C, Lichtenstein E, Khan K, Atkins L, Rada A, Kim HA, Chiuzan C, Kalac M, Marchi E, Falchi L, Francescone MA, Schwartz L, Cremers S, O'Connor OA. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood. 2018 Jan 25;131(4):397-407. doi: 10.1182/blood-2017-09-806737. Epub 2017 Nov 15.
Results Reference
derived

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Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies

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