Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies

NCT ID: NCT01947140

Last Updated: 2022-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-09
• Study Completion Date: 2022-09-01

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Pralatrexate

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Pralatrexate

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Pralatrexate

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Folotyn; Istodax

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jennifer Amengual

OTHER

Sponsor Role: lead

Responsible Party

Jennifer Amengual

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jennifer Amengual, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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, United States

Countries

United States

References

Ryu Tiger YK, Jain S, Barta SK, Tolu S, Estrella B, Sawas A, Lue JK, Francescone MM, Pro B, Amengual JE. Phase II study of the novel antifolate agent pralatrexate in combination with the histone deacetylase inhibitor romidepsin for the treatment of patients with mature T-cell lymphoma. Leuk Lymphoma. 2024 Jun;65(6):736-745. doi: 10.1080/10428194.2024.2329996. Epub 2024 Mar 22.

Reference Type: DERIVED

PMID: 38517235 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29141948 (View on PubMed)

Other Identifiers

AAAJ5656

Identifier Type: -

Identifier Source: org_study_id