Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies

Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01947140
• Other study ID #: AAAJ5656
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 9, 2013
• Est. completion date: September 1, 2022

Study information

• Verified date: November 2022
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: September 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoid Malignancies
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms
• Non-hodgkin Lymphoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Columbia University Irving Medical Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Jennifer Amengual

Country where clinical trial is conducted

United States, 

Outcome

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