Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies

NCT01947140 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AAAJ5656
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 3

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).

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin

  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

  For Phase II

  Up to 3 years

Secondary Outcomes (9)

• Maximum number of cycles received

  Up to 1.5 years

• Number of dose delays at the MTD

  Up to 1.5 years

• Overall response rate (ORR) of the study population

  Up to 1.5 years

• Duration of response (DOR) of the combination in patients with T-Cell Lymphoma

  Up to 3 years

• Overall survival (OS) of patients with T-Cell Lymphoma on study

  Up to 3 years

Study Arms (3)

Phase I: Schedule A

EXPERIMENTAL

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

Drug: Pralatrexate; Drug: Romidepsin

Phase I: Schedule B

EXPERIMENTAL

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

Drug: Pralatrexate; Drug: Romidepsin

Phase II

EXPERIMENTAL

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; Drug: Romidepsin

Interventions

Pralatrexate 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.

Also known as: Folotyn

Phase I: Schedule A; Phase I: Schedule B; Phase II

Romidepsin 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.

Also known as: Istodax

Phase I: Schedule A; Phase I: Schedule B; Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jennifer Amengual: lead

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Columbia University Irving Medical Center

New York, New York, 10019, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (2)

• 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.

  PMID: 38517235 DERIVED

• 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.

  PMID: 29141948 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Burkitt Lymphoma; Waldenstrom Macroglobulinemia; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous

Interventions

10-propargyl-10-deazaaminopterin; romidepsin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphatic Diseases; Lymphoma, B-Cell; Lymphoma, T-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Jennifer Amengual, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 9, 2013
• First Posted: September 20, 2013
• Study Start: September 9, 2013
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: November 23, 2022

Record last verified: 2022-11

Locations

US (3)