Clinical Trials /

Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies

NCT01947140

Description:

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).

Related Conditions:
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
  • T-Cell Lymphoblastic Leukemia/Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
  • 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 Relapsed and Refractory Lymphoid Malignancies and Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: AAAJ5656
  • NCT ID: NCT01947140

Conditions

  • Lymphoid Malignancies
  • Multiple Myeloma
  • Lymphoma
  • Hodgkin Lymphoma
  • Non-hodgkin Lymphoma

Interventions

DrugSynonymsArms
PralatrexateFolotynPhase I: Schedule A
RomidepsinIstodaxPhase I: Schedule A

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I: Schedule AExperimentalSubjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle
  • Pralatrexate
  • Romidepsin
Phase I: Schedule BExperimentalSubjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle
  • Pralatrexate
  • Romidepsin
Phase IIExperimentalSubjects 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
  • Pralatrexate
  • Romidepsin

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin
Time Frame:Up to 1.5 years
Safety Issue:
Description:For Phase I

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jennifer Amengual

Trial 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

Last Updated

February 14, 2017