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

This study is currently recruiting participants.
Verified September 2013 by The Lymphoma Academic Research Organisation
Sponsor:
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT01280526
First received: January 14, 2011
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

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.

Condition Intervention Phase
Peripheral T Cell Lymphoma
Drug: Romidepsin and CHOP
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by The Lymphoma Academic Research Organisation:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Complete Response Rate(CR) at the end of treatment [ Time Frame: 30 days after the end of treatment ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: from the date of inclusion to the date of first documentated disease progression, relapse or death from any cause ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: from the date of first documentation of a response to the date of first documented evidence of progression/relapse or death from any cause ] [ Designated as safety issue: No ]
  • Safety of association Romidepsin-CHOP [ Time Frame: from the date of informed consent signature to 90 days after the last drug administration ] [ Designated as safety issue: Yes ]
    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.

  • Overall Response at the end of treatment [ Time Frame: 30 days after the end of treatment ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: from the date of inclusion to the date of first documentated disease progression, relapse or death from any cause ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2011
Estimated Study Completion Date: January 2014
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Romidepsin dose 10mg/m²
Romidepsin dose 10mg/m²
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
Experimental: Romidepsin dose 12mg/m²
Romidepsin dose 12mg/m²
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
Experimental: Romidepsin dose 14mg/m²
Romidepsin dose 14mg/m²
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
Experimental: Romidepsin dose 8mg/m²
Romidepsin dose 8mg/m²
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

Detailed 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.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01280526

Contacts
Contact: Sabine BALOUET, PM +33(0)472669333 sabine.balouet@gelarc.org
Contact: Yvain ROBREAU, PM +33(0)472669333 yvain.robreau@gelarc.org

Locations
France
Hôpital Henri Mondor Recruiting
Créteil, France, 94010
Contact: Jehan DUPUIS, MD       jehan.dupuis@hmn.aphp.fr   
Principal Investigator: Jehan DUPUIS, MD         
CHU de Dijon Recruiting
Dijon, France, 21000
Contact: Olivier CASASNOVAS, MD       olivier.casasnovas@chu-dijon.fr   
Principal Investigator: Olivier CASASNOVAS, MD         
Hôpital Claude Huriez Recruiting
Lille, France, 59037
Contact: Franck MORSCHHAUSER, MD       f-morschhauser@chru-lille.fr   
Principal Investigator: Franck MORSCHHAUSER, MD         
Centre Léon Bérard Recruiting
Lyon cedex 8, France, 69373
Contact: Hervé GHESQUIERES, MD       GHESQUIE@lyon.fnclcc.fr   
Principal Investigator: Hervé GHESQUIERES, MD         
Hôpital St Louis Recruiting
Paris, France, 75475
Contact: Catherine THIEBLEMONT, Professor       catherine.thieblemont@sls.ap-hop-paris.fr   
Principal Investigator: Catherine THIEBLEMONT, Professor         
Centre Hospitalier Lyon Sud Recruiting
Pierre-Bénite, France, 69495
Contact: Bertrand COIFFIER, Professor       bertrand.coiffier@chu-lyon.fr   
Principal Investigator: Bertrand COIFFIER, Professor         
Centre Henri Becquerel Recruiting
Rouen, France, 76038
Contact: Hervé TILLY, Professor       herve.tilly@rouen.fnclcc.fr   
Principal Investigator: Hervé TILLY, Professor         
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Vincent RIBRAG, MD       vincent.ribrag@igr.fr   
Principal Investigator: Vincent RIBRAG, MD         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Investigators
Principal Investigator: Bertrand COIFFIER, Professor
  More Information

No publications provided

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT01280526     History of Changes
Other Study ID Numbers: Ro-CHOP
Study First Received: January 14, 2011
Last Updated: September 25, 2013
Health Authority: France: ANSM : Agence Nationale de sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Romidepsin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 14, 2014