Clinical trial NCT01846390: Romidepsin, Gemcitabine, Dexamethasone and Cisplatin in the Treatment of Peripheral T-Cell and Diffuse Large B-Cell Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Peripheral T-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Celgene
First posted: 2013-05-03
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: The purpose of this study is to find the highest dose of romidepsin that can safely be given in combination with gemcitabine, dexamethasone, and cisplatin (GDP) without causing very severe side effects that are not tolerable. This is done by starting at a dose lower than the one that does not cause side effects in animals. Patients are given romidepsin and GDP and watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then more patients are asked to join the study and are given a higher dose of romidepsin (with GDP). Patients joining the study later on will get higher doses of romidepsin (with GDP) than patients who join earlier. This will continue until a dose is found that causes severe but temporary side effects. Doses higher than that will not be given.

Eligibility criteria: Inclusion Criteria:

* 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.

  * Calculated creatinine clearance (Cockcroft-Gault formula) of ≥ 50 mL /min.
  * Women must be post-menopausal, surgically sterile or use reliable forms of contraception while on study and for 90 days after discontinuing therapy. Women of childbearing potential must have a pregnancy test taken and proven negative within 7 days prior to registration and must not be lactating.
  * Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements.
  * Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial.
  * In accordance with NCIC CTG policy, protocol treatment is to begin within 2 working days of patient registration.

Exclusion Criteria:

* 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.
* Patients with active or uncontrolled infections, or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol are not eligible.
* Patients are not eligible if they have a known hypersensitivity to the study drugs or their components.

Primary outcomes:
measure: Maximum tolerated dose of combined romidepsin, gemcitabine, dexamethasone and cisplatin.
timeFrame: 48 months
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: 48 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Saint John
country: Canada
facility: Regional Health Authority B, Zone 2
state: New Brunswick
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Atlantic Health Sciences Corp - Saint John Regional Hospital, Saint John NB Canada
name: Anthony J Reiman
role: STUDY_CHAIR
affiliation: BCCA Vancouver Cancer Centre, Vancouver BC Canada
name: Kerry J Savage
role: STUDY_CHAIR
References:
citation: 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.