Romidepsin, Gemcitabine, Dexamethasone and Cisplatin in the Treatment of Peripheral T-Cell and Diffuse Large B-Cell Lymphoma

NCT01846390 | Completed Phase 1 DMC

• 1 other identifier: LY15
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

Brief Summary

This research is being done because it is not yet known what dose of romidepsin in combination with gemcitabine, dexamethasone, and cisplatin (GDP) can be given safely to patients with peripheral T-cell lymphoma, nor what type and severity of side effects will result from the combination of these treatments. This research is also being done because it is not clear if the addition of the new drug romidepsin to treatment with GDP can offer better results and longer survival.

Conditions

Peripheral T-Cell Lymphoma; Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of combined romidepsin, gemcitabine, dexamethasone and cisplatin.

  Combination of GDP with romidepsin at the maximum tolerated doses of these agents will identify the combination regimen for comparison in the subsequent randomized phase II trial; if romidepsin appears to improve the activity of GDP, then this will move forward to a formal phase III comparison to CHOP. Primary end points are toxicity, the maximum administered dose and the recommended phase II dose.

  48 months

Secondary Outcomes (1)

• Number of patients with adverse events

  48 months

Study Arms (1)

romidepsin, gemcitabine, dexamethasone and cisplatin

EXPERIMENTAL

A traditional phase I dose escalation design is proposed to assess the feasibility and tolerability of romidepsin in combination with GDP, where treatment will be escalated. Treatment will be given for 6 cycles unless there is evidence of progression prior to completion of the 6 cycles or tolerability to the regimen is not sustained.

Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin; Drug: Romidepsin

Interventions

Gemcitabine DRUG

Group 1 = 1000 mg/m2 D1, D8. Subsequent dose levels according to toxicity = 600-1000 mg/m2 D1, D15.

romidepsin, gemcitabine, dexamethasone and cisplatin

Dexamethasone DRUG

40 mg D1 - D4

romidepsin, gemcitabine, dexamethasone and cisplatin

Cisplatin DRUG

75 mg/m2 D1

romidepsin, gemcitabine, dexamethasone and cisplatin

Romidepsin DRUG

Dose Level 0 - 6 mg/m2 D1, D8. Subsequent dose levels according to toxicity 6-14 mg/m2 D1, D15.

romidepsin, gemcitabine, dexamethasone and cisplatin

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed PTCL. Biopsy proof of disease at initial diagnosis is mandatory. A biopsy at relapse is preferred but not mandatory.
• Patients must have received one or two previous regimens of therapy for their disease (salvage chemotherapy plus autologous stem cell transplantation is considered to be one regimen).
• Clinically and / or radiologically measurable disease (1 site bidimensionally measurable). Measurements / evaluations must be done within 28 days prior to registration.
• Age 18 to 75 years.
• ECOG performance status 0, 1 or 2.
• Life expectancy of ≥ 90 days (3 months).
• Laboratory Requirements: (must be done within 7 days of registration)
• Hematology:
• Granulocytes (AGC) ≥ 1.0 x 10\^9/L
• Platelets ≥ 75 x 10\^9/L (≥ 50 if bone marrow involvement by lymphoma)
• Biochemistry:
• AST and ALT ≤ 2.5x ULN (≤ 5x ULN if hepatic involvement of disease)
• Serum total bilirubin ≤ 1.5x ULN (≤ 3x ULN if hepatic involvement of disease, or ≤5x ULN if Gilberts Disease)
• Serum Potassium ≥ 3.8 mmol/L\*
• Serum Magnesium ≥ 0.85 mmol/L\* \* NB: Patients with potassium and magnesium levels below these values are eligible if supplementation has corrected these deficits. This supplementation should continue throughout the course of the study.

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast or localized excised prostate cancer, or other solid tumours curatively treated with no evidence of disease for ≥ 3 years.
• Central nervous system involvement, meningeal or parenchymal. Patients with CNS disease at initial presentation and who are in a CNS CR at the time of relapse are eligible. MRI scanning and / or lumbar puncture should be performed if there is clinical suspicion of active CNS disease.
• HIV, active hepatitis B or current hepatitis C infection. (Hepatitis B core antibody positive, surface antigen negative patients allowed if concurrent anti-viral prophylaxis is administered. Patients with a past history of hepatitis C who have eradicated the virus are eligible.)
• Any serious active disease or co-morbid medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating (according to investigator's decision).
• Patients with serious cardiac illness or condition including, but not limited to:
• history of documented congestive heart failure (CHF)
• systolic dysfunction (LVEF \< 45% by MUGA or ECHO)
• high risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled)
• unstable angina pectoris requiring anti-anginal medication
• clinically significant valvular heart disease
• evidence of transmural infarction on ECG
• New York Heart Association (NYHA) Class III or IV functional status
• patients with congenital long QT syndrome, history of significant cardiovascular disease and/or taking drugs leading to significant QT prolongation
• patients with QTc \> 480 msec are not eligible
• Pregnant or lactating females or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study.

Sponsors & Collaborators

• Celgene: collaborator
• Canadian Cancer Trials Group: lead

Study Sites (6)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Reiman T, Savage KJ, Crump M, Cheung MC, MacDonald D, Buckstein R, Couban S, Piliotis E, Imrie K, Spaner D, Shivakumar S, Kuruvilla J, Villa D, Shepherd LE, Skamene T, Winch C, Chen BE, Hay AE. A phase I study of romidepsin, gemcitabine, dexamethasone and cisplatin combination therapy in the treatment of peripheral T-cell and diffuse large B-cell lymphoma; the Canadian cancer trials group LY.15 studydagger. Leuk Lymphoma. 2019 Apr;60(4):912-919. doi: 10.1080/10428194.2018.1515937. Epub 2018 Oct 10.

  PMID: 30301414 RESULT

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Lymphoma, Large B-Cell, Diffuse

Interventions

Gemcitabine; Dexamethasone; Cisplatin; romidepsin

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Anthony J Reiman

  Atlantic Health Sciences Corp - Saint John Regional Hospital, Saint John NB Canada

  STUDY CHAIR

• Kerry J Savage

  BCCA Vancouver Cancer Centre, Vancouver BC Canada

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: May 3, 2013
• Study Start: October 1, 2013
• Primary Completion: July 6, 2016
• Study Completion: September 19, 2018
• Last Updated: March 27, 2026

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)