A Study of Escalating Doses of Romidepsin in Association With CHOP in the Treatment of Peripheral T-Cell Lymphomas

Peripheral T Cell Lymphoma Clinical Trial

— Ro-CHOP  

Official title:

A Phase IB/II Study of Escalating Doses of Romidepsin (Istodax®) in Association With CHOP (Ro-CHOP) in the Treatment of Peripheral T-Cell Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01280526
• Other study ID #: Ro-CHOP
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 14, 2011
• Last updated: May 21, 2014
• Start date: January 2011
• Est. completion date: March 2014

Study information

• Verified date: May 2014
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: ANSM : Agence Nationale de sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

This study is an open label, multicenter study with two phases:

• A dose escalation phase of Romidepsin administered IV at day 1 and 8 or at day 1 without day 8 in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)administered every 3 weeks for 8 cycles in patients with T-cell lymphoma.

• An expansion phase in order to assess the safety and the efficacy of the association of the recommended dose of Romidepsin associated with CHOP in a population of patients with T-cell lymphoma.

Description:

The primary objective of the study is to determine the feasibility of the combination and the recommended dose (RD) of Romidepsin when administered in association with CHOP in a population of patients with newly diagnosed Peripheral T-cell lymphoma (PTCL) as measured by the toxicities during treatment.

Secondary objectives:

• To assess the safety of the association Romidepsin and CHOP,

• To assess the efficacy of the association of Romidepsin and CHOP: response rate and complete response rate, progression-free survival, response duration and overall survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 2014
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

1. Inclusion Criteria:

1. Patients with histologically confirmed Peripheral T-cell Lymphoma (PTCL), not previously treated ; all subtypes may be included except HTLV-1-related T-cell lymphoma, cutaneous T-cell lymphoma (mycosis fungoid and Sézary syndrome), and ALK+ PTCL,

2. Ann Arbor stages II - IV

3. Aged from 18 to 80 years,

4. ECOG performance status 0, 1 or 2,

5. Signed informed consent,

6. Negative pregnancy test for females of childbearing potential (FCBP),

7. FCBP using an effective method of birth control (i.e. hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide or abstinence) for the treatment period and for 1 month thereafter; Males using an effective method of birth control for the treatment period and 3 months thereafter,

8. Life expectancy of = 90 days (3 months)

2. Exclusion Criteria:

1. Other types of lymphomas, e.g. B-cell lymphoma

2. Ann Arbor stage I

3. Previous treatment for PTCL with immunotherapy or chemotherapy except for short-term corticosteroids before inclusion

4. Previous radiotherapy for PTCL except if localized to one lymph node area

5. Central nervous system - meningeal involvement

6. Contraindication to any drug contained in the chemotherapy regimen

7. HIV infection, active hepatitis B or C

8. Any serious active disease or co-morbid medical condition (according to investigator's decision)

9. Any of the following laboratory abnormalities

• Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L),

• Platelet count < 100,000/mm3 (100 x 109/L), or 75,000 if bone marrow is involved,

• Serum SGOT/AST or SGPT/ALT = 5.0 x upper limit of normal (ULN),

• Serum total bilirubin > 2.0 mg/dL (34 µmol/L), except in case of hemolytic anemia,

• Low K+ (inferior to low normal level) and low Mg+ (inferior to low normal level)levels, except if corrected before beginning the chemotherapy,

10. Use of oral contraceptive and contraceptive patches,

11. Calculated creatinine clearance (Cockcroft-Gault formula) of < 50 mL /min,

12. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for = 3 years,

13. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form,

14. Left Ventricular Ejection Fraction < 45% (calculated by echocardiographic or scintigraphic methods),

15. Patients with congenital long QT syndrome, history of significant cardiovascular disease and/or taking drugs leading to significant QT prolongation,

16. Corrected QT interval > 480 msec (using the fridericia formula)

17. Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug ,

18. Pregnant or lactating females or women of childbearing potential not will-ing to use an adequate method of birth control for the duration of the study.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma

Intervention

Drug:
• Romidepsin and CHOP
Romidepsin dose administered IV at day 1 and 8 or at day 1 without day 8 in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered every 3 weeks for 8 cycles in patients with T-cell lymphoma
• Romidepsin and CHOP
Romidepsin dose administered IV at day 1 and 8 or at day 1 without day 8 in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered every 3 weeks for 8 cycles in patients with T-cell lymphoma
• Romidepsin and CHOP
Romidepsin dose administered IV at day 1 and 8 or at day 1 without day 8 in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered every 3 weeks for 8 cycles in patients with T-cell lymphoma
• Romidepsin and CHOP
Romidepsin dose administered IV at day 1 and 8 or at day 1 without day 8 in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered every 3 weeks for 8 cycles in patients with T-cell lymphoma

Locations

Country	Name	City	State
France	Hôpital Henri Mondor	Créteil
France	CHU de Dijon	Dijon
France	Hôpital Claude Huriez	Lille
France	Centre Léon Bérard	Lyon cedex 8
France	Hôpital St Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Centre Henri Becquerel	Rouen
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities		42 days	Yes
Secondary	Complete Response Rate(CR) at the end of treatment		30 days after the end of treatment	No
Secondary	Progression-free survival (PFS)		from the date of inclusion to the date of first documentated disease progression, relapse or death from any cause	No
Secondary	Duration of Response		from the date of first documentation of a response to the date of first documented evidence of progression/relapse or death from any cause	No
Secondary	Safety of association Romidepsin-CHOP	Toxicities occured during the trial for all patient from the date of informed consent signature to 90 days after the last drug administration will be measured and reported for all grades toxicities according to CTCAE v4.	from the date of informed consent signature to 90 days after the last drug administration	Yes
Secondary	Overall Response at the end of treatment		30 days after the end of treatment	No
Secondary	Overall Survival (OS)		from the date of inclusion to the date of first documentated disease progression, relapse or death from any cause	No