Phase I Study of Romidepsin, Gemcitabine, Oxaliplatin, and Dexamethasone in Patients With Relapsed/Refractory Aggressive Lymphomas

NCT02181218 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201407160
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to find the maximum tolerated dose of a drug called romidepsin when given with a treatment regimen called GemOxD. GemOxD is a routine treatment for certain types of lymphoma, and involves the administration of three drugs: gemcitabine, oxaliplatin, and dexamethasone. In addition to finding the maximum tolerated dose of romidepsin, the investigators want to look at the side effects of these drugs when given together, as well as how the lymphoma responds to this treatment.

Conditions

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral; Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (recommended Phase II dose)

  Three participants will be treated at each dose level. If 0/3 patients experience dose limiting toxicity (DLT), 3 patients will be treated at the next dose level. If a DLT attributable to the treatment is experienced in 1 of 3 patients, three more patients (for a total of six participants) will be treated at that dose level. If no additional DLTs are observed at the expanded dose level (i.e. 1 of 6 with DLT), the dose will be escalated. Escalation will terminate as soon as two or more participants experience any DLT attributable to study combination, at a given dose level. If 2 or more DLTs occur at the starting dose level, a decreased dose level will be explored at dose level -1. There will be no more than 2 patients dosed for the first time within the same week, and patients in the next higher cohorts will not be enrolled until the last patient of the lower cohort has completed the DLT monitoring period, defined as 21 days after first dose of Cycle 1 therapy.

  37 months (completion of first cycle of all participants in study)

Secondary Outcomes (5)

• Complete response rate

  Up to 1 year from time of maximal response

• Partial response rate

  Up to 1 year from time of maximal response

• Overall response rate

  Up to 1 year from time of maximal response

• Progression free survival

  Up to 1 year from time of maximal response

• Duration of response

  Up to 1 year from time of maximal response

Study Arms (3)

Dose Level 0 (starting dose) (8 mg/m2 romidepsin)

EXPERIMENTAL

* Romidepsin will be administered intravenously (IV) over 2 hours on Days 2 and 8; * Gemcitabine IV over 30 minutes on Day 1 * Oxaliplatin IV over 2 hours on Day 1 * Dexamethasone orally on Days 1-4 * Pegfilgrastim subcutaneously on Day 3 * Drugs may be administered in any order on Day 1. * Each cycle is 21 days. * May continue on therapy for up to 8 cycles total if achieving adequate disease control (CR, PR, or stable disease) and without significant toxicity

Drug: Romidepsin; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Dexamethasone; Drug: Pegfilgrastim

Dose Level 1 (10 mg/m2 romidepsin)

EXPERIMENTAL

* Romidepsin will be administered intravenously (IV) over 2 hours on Days 2 and 8; * Gemcitabine IV over 30 minutes on Day 1 * Oxaliplatin IV over 2 hours on Day 1 * Dexamethasone orally on Days 1-4 * Pegfilgrastim subcutaneously on Day 3 * Drugs may be administered in any order on Day 1. * Each cycle is 21 days. * May continue on therapy for up to 8 cycles total if achieving adequate disease control (CR, PR, or stable disease) and without significant toxicity

Drug: Romidepsin; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Dexamethasone; Drug: Pegfilgrastim

Dose Level 2 (12 mg/m2 romidepsin)

EXPERIMENTAL

* Romidepsin will be administered intravenously (IV) over 2 hours on Days 2 and 8; * Gemcitabine IV over 30 minutes on Day 1 * Oxaliplatin IV over 2 hours on Day 1 * Dexamethasone orally on Days 1-4 * Pegfilgrastim subcutaneously on Day 3 * Drugs may be administered in any order on Day 1. * Each cycle is 21 days. * May continue on therapy for up to 8 cycles total if achieving adequate disease control (CR, PR, or stable disease) and without significant toxicity

Drug: Romidepsin; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Dexamethasone; Drug: Pegfilgrastim

Interventions

Romidepsin DRUG

Also known as: Istodax®

Dose Level 0 (starting dose) (8 mg/m2 romidepsin); Dose Level 1 (10 mg/m2 romidepsin); Dose Level 2 (12 mg/m2 romidepsin)

Gemcitabine DRUG

Also known as: GEMZAR®

Dose Level 0 (starting dose) (8 mg/m2 romidepsin); Dose Level 1 (10 mg/m2 romidepsin); Dose Level 2 (12 mg/m2 romidepsin)

Oxaliplatin DRUG

Also known as: Eloxatin TM

Dose Level 0 (starting dose) (8 mg/m2 romidepsin); Dose Level 1 (10 mg/m2 romidepsin); Dose Level 2 (12 mg/m2 romidepsin)

Dexamethasone DRUG

Also known as: Decadron®, Dexamethasone Intensol®, Dexpak® Taperpak®

Dose Level 0 (starting dose) (8 mg/m2 romidepsin); Dose Level 1 (10 mg/m2 romidepsin); Dose Level 2 (12 mg/m2 romidepsin)

Pegfilgrastim DRUG

Also known as: Neulasta®

Dose Level 0 (starting dose) (8 mg/m2 romidepsin); Dose Level 1 (10 mg/m2 romidepsin); Dose Level 2 (12 mg/m2 romidepsin)

Eligibility Criteria

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

You may qualify if:

• Able to understand and voluntarily sign an informed consent form
• Age ≥ 18 at time of informed consent
• Diagnosis of one of the following:
• relapsed/refractory peripheral T-cell lymphoma of any subtype including mycosis fungoides and Sézary syndrome of advanced stage (IIB-IVB)
• \*\*for the expansion cohort:patients must have biopsy-proven T-cell lymphoma and measurable disease.
• relapsed/refractory DLBCL (up to 6 DLBCL patients are allowed in the dose-escalation portion of the study)
• relapsed/refractory HL
• Note: extracorporeal photopheresis is NOT considered a systemic therapy for this study.
• Transplant eligible (as determined by referring physician) patients who have failed one prior salvage therapy or transplant ineligible (as determined by referring physician) patients who have failed one prior therapy
• ECOG performance status of ≤ 2
• Laboratory test results within the following ranges:
• Absolute neutrophil count ≥ 1500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 x ULN
• AST (SGOT) and ALT (SGPT) ≤ 3 x ULN

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would - in the opinion of the investigator - prevent the subject from signing the informed consent form
• Pregnant or lactating women
• Any medical condition or laboratory abnormalities, which - in the opinion of the investigator - places the subject at unacceptable risk, or confounds the ability to interpret data if he/she were to participate in the study
• Positive CSF cytology during staging, symptomatic leptomeningeal involvement, or parenchymal involvement of brain or spinal cord
• Prior allogeneic hematopoietic cell transplant
• Prior solid organ transplant
• Cirrhotic liver disease from any cause
• Known HIV infection
• Impaired cardiac function or clinically significant cardiac disease including any of the following:
• Congenital long QT syndrome
• Screening ECG with QTc interval ≥ 500 milliseconds
• Myocardial infarction (MI) or unstable angina ≤ 6 months of C1D1; however, subjects with a history of MI between 6 and 12 months who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event would be eligible
• Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
• An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
• Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (defined here as ventricular rate \< 50 bpm); right bundle-branch block + left anterior hemi-block (bifasicular block)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Celgene: collaborator

Study Sites (2)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Foley N, Riedell PA, Bartlett NL, Cashen AF, Kahl BS, Fehniger TA, Fischer A, Moreno C, Liu J, Carson KR, Mehta-Shah N. A Phase I Study of Romidepsin in Combination With Gemcitabine, Oxaliplatin, and Dexamethasone in Patients With Relapsed or Refractory Aggressive Lymphomas Enriched for T-Cell Lymphomas. Clin Lymphoma Myeloma Leuk. 2025 May;25(5):328-336. doi: 10.1016/j.clml.2024.11.015. Epub 2024 Dec 4.

  PMID: 39725584 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral; Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse

Interventions

romidepsin; Gemcitabine; Oxaliplatin; Dexamethasone; Calcium Dobesilate; pegfilgrastim

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Neha Mehta-Shah, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2014
• First Posted: July 3, 2014
• Study Start: February 4, 2015
• Primary Completion: March 28, 2019
• Study Completion: June 26, 2020
• Last Updated: November 17, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)