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

• ClinicalTrials.gov Identifier: NCT01947140
• Recruitment Status: Completed
• First Posted: September 20, 2013
• Last Update Posted: November 23, 2022
• Sponsor: Jennifer Amengual
• Information provided by (Responsible Party): Jennifer Amengual, Columbia University

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).

Condition or disease	Intervention/treatment	Phase
Lymphoid Malignancies; Multiple Myeloma; Lymphoma; Hodgkin Lymphoma; Non-hodgkin Lymphoma	Drug: Pralatrexate; Drug: Romidepsin	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 9, 2013
• Actual Primary Completion Date: September 1, 2022
• Actual Study Completion Date: September 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	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.; Other Name: Folotyn; 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.; Other Name: Istodax
Experimental: 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	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.; Other Name: Folotyn; 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.; Other Name: Istodax
Experimental: 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	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.; Other Name: Folotyn; 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.; Other Name: Istodax

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin [ Time Frame: Up to 1.5 years ]
   For Phase I
2. Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma [ Time Frame: Up to 3 years ]
   For Phase II

Secondary Outcome Measures :

1. Maximum number of cycles received [ Time Frame: Up to 1.5 years ]
   For Phase II
2. Number of dose delays at the MTD [ Time Frame: Up to 1.5 years ]
   For Phase I
3. Overall response rate (ORR) of the study population [ Time Frame: Up to 1.5 years ]
   For Phase I
4. Duration of response (DOR) of the combination in patients with T-Cell Lymphoma [ Time Frame: Up to 3 years ]
   For Phase II
5. Overall survival (OS) of patients with T-Cell Lymphoma on study [ Time Frame: Up to 3 years ]
   For Phase II
6. Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma [ Time Frame: Up to 3 years ]
   For Phase II
7. Number of dose reductions at the MTD [ Time Frame: Up to 1.5 years ]
   For Phase I
8. Progression free survival (PFS) of the study population [ Time Frame: Up to 1.5 years ]
   For Phase I
9. Duration of response (DOR) of the study population. [ Time Frame: Up to 1.5 years ]
   For Phase I

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, New York

Columbia University Irving Medical Center

New York, New York, United States, 10019

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

Sponsors and Collaborators

Jennifer Amengual

Investigators

• Principal Investigator: Jennifer Amengual, MD; Columbia University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jennifer Amengual, Assistant Professor of Medicine, Columbia University
• ClinicalTrials.gov Identifier: NCT01947140
• Other Study ID Numbers: AAAJ5656
• First Posted: September 20, 2013
• Last Update Posted: November 23, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jennifer Amengual, Columbia University:

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

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Neoplasms; Lymphoma, Non-Hodgkin; Hodgkin Disease; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Romidepsin; Antibiotics, Antineoplastic; Antineoplastic Agents