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Ro Plus CHOEP as First Line Treatment Before HSCT in Young Patients With Nodal Peripheral T-cell Lymphomas (FIL_PTCL13)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02223208
Recruitment Status : Recruiting
First Posted : August 22, 2014
Last Update Posted : March 20, 2020
Sponsor:
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

Brief Summary:

This is a multicenter study that includes two phases:

  1. A phase I study to define the maximum tolerated dose (MTD) of Romidepsin in addition to CHOEP-21 and to test the safety and feasibility of CHOEP-21 in combination with dose escalation of Romidepsin (8, 10, 12, 14 mg). The dose level defined as MTD of Romidepsin will be used for the subsequent phase II study.
  2. A phase II study to evaluate the efficacy (response rate, progression free survival and overall survival) and safety of Ro-CHOEP-21 incorporated into a treatment strategy including SCT.

Condition or disease Intervention/treatment Phase
Peripheral T-cell Lymphomas (PTCL) PTCL-NOS Angioimmunoblastic T-cell Lymphoma (AITL) ALK- Anaplastic Large Cell Lymphoma (ALCL) Nodal Peripheral T-Cell Lymphoma of T Follicular Helper Cell Origin Drug: Ro-CHOEP-21 (PHASE I) Drug: Ro-CHOEP-21 (PHASE II) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Romidepsin in Combination With CHOEP as First Line Treatment Before Hematopoietic Stem Cell Transplantation in Young Patients With Nodal Peripheral T-cell Lymphomas: a Phase I-II Study
Actual Study Start Date : September 2014
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : March 2027


Arm Intervention/treatment
Experimental: Ro-CHOEP-21
During the Phase I It will administered Romidepsin (dose escalation) and the combination of CHOEP-21. During the Phase II It will administered Romidepsin (dose according to phase I) and the combination of CHOEP-21.
Drug: Ro-CHOEP-21 (PHASE I)

Romidepsin (dose escalation) Starting dose: 12mg/ms iv day +1 and +8

Dose modification according to toxicity:

  • 14mg/ms day +1 and +8
  • 10mg/ms day +1 and +8
  • 8mg/ms day +1 and +8

CHOEP-21

  • Doxorubicin 50 mg/ms iv day +1 or +2,
  • Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2
  • Cyclophosphamide 750 mg/ms iv day +1 or +2
  • Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4
  • Prednisone100 mg orally from days +1 to +5 or from days +2 to +6

PR or CR:Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --> AUTO-SCT, PR --> ALLO-SCT)

Other Names:
  • Romidepsin
  • Cyclophosphamide
  • Doxorubicin
  • Vincristin
  • Etoposide
  • Prednisone

Drug: Ro-CHOEP-21 (PHASE II)

Ro-CHOEP-21 x 3 cycles

  • Romidepsin dose according to phase I iv day +1 and +8
  • Doxorubicin 50 mg/ms iv day +1 or +2,
  • Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2,
  • Cyclophosphamide 750 mg/ms iv day +1 or +2
  • Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4
  • Prednisone100 mg orally from days +1 to +5 or from days +2 to +6

PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --> AUTO-SCT, PR --> ALLO-SCT)

Other Names:
  • Romidepsin
  • Cyclophosphamide
  • Doxorubicin
  • Vincristin
  • Etoposide
  • Prednisone




Primary Outcome Measures :
  1. Dose-limiting toxicity (DLT) of Ro-CHOEP-21 (Phase I endpoint) [ Time Frame: 3 months ]
    Incidence of dose-limiting toxicity (DLT) of Ro-CHOEP-21, considering as maximum dose the one causing induction of any grade ≥ 3 non hematologic toxicity or a delay >15 days of planned cycle date observed during the first two cycles according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)

  2. Progression Free Survival (PFS) of Ro-CHOEP-21 (Phase II endpoint) [ Time Frame: 18 months ]
    PFS on intention to treatment (ITT) evaluated at 18 months. PFS will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause.


Secondary Outcome Measures :
  1. Proportion of patients reaching SCT (Phase I endpoint) [ Time Frame: 6 months ]
    Proportion of patients reaching SCT

  2. ORR = Overall response rate (Phase I endpoint) [ Time Frame: 6 months ]
    Overall response rate (ORR, defined according to the Cheson 2007 response criteria) of the combination of Ro-CHOEP-21.

  3. Overall Response Rate (ORR) and Complete Response (CR)(Phase II endpoint) [ Time Frame: 6 months ]
    ORR and CR (defined according to the Cheson 2007 response criteria), after induction treatment and after SCT.

  4. Event free survival (EFS) (Phase II endpoint) [ Time Frame: 18 months ]
    Event free survival (EFS) defined as the time between the date of enrollment and the date of discontinuation of treatment for any reason

  5. Overall survival (OS) (Phase II endpoint) [ Time Frame: 24 months ]
    Overall survival (OS) defined as the time between the date of enrolment and the date of death from any cause in the ITT population enrolled in the study

  6. Progression Free Survival (PFS) and Overall Survival (OS) (Phase II endpoint) [ Time Frame: 3 months ]
    PFS and OS in patients not responding to the first 3 courses of Ro-CHOEP-21

  7. Toxicities (Phase II endpoint) [ Time Frame: 18 months ]
    Evaluation during the interim analyses of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)

  8. Higher toxicities (Phase II endpoint) [ Time Frame: 18 months ]
    Evaluation during all the pretransplant phase of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)

  9. Treatment-related mortality (TRM) (Phase II Endpoint) [ Time Frame: 24 months ]
    Treatment-related mortality defined as any death that was not attributable to the lymphoma.

  10. Graft-versus-host disease (GVHD) (Phase II endpoint) [ Time Frame: 24 months ]
    Incidence of acute and chronic GVHD in allografted patients


Other Outcome Measures:
  1. Evaluation of response biomarkers (eg TET2 mutations) [ Time Frame: 8 years ]
    Evaluation of response biomarkers (eg TET2 mutations)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 e ≤ 65 years
  2. Peripheral T-cell lymphomas at diagnosis including: PTCL-NOS, AITL including other nodal TFH, ALK-ALCL
  3. Stage II-IV
  4. Written informed consent
  5. No prior treatment for lymphoma
  6. No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
  7. HIV negativity
  8. Absence of active hepatitis C virus (HCV) infection
  9. HBV negativity or patients with HBcAb +, HBsAg -, HBs Ab+/- with HBV-DNA negativity (in these patients Lamivudine prophylaxis is mandatory)
  10. Levels of serum bilirubin, alkaline phosphatase and transaminases < 2 the upper normal limit, if not disease related
  11. No psychiatric illness that precludes understanding concepts of the trial or signing informed consent
  12. Ejection fraction > 50% and myocardial stroke in the last year nor QT prolongation (QTc interval < 480 msec using the Fridericia formula)
  13. Clearance of creatinine > 60 ml/min if not disease related
  14. Spirometry Diffusion Capacity (DLCO) > 50%
  15. Absence of active, uncontrolled infection
  16. For males and females of child-bearing potential, agreement upon the use of effective contraceptive methods prior to study entry, for the duration of study participation and in the following 90 days after discontinuation of study treatment
  17. Availability of histological material for central review and pathobiological studies.

Exclusion Criteria:

  1. Age <18 e > 65 years
  2. Hystology other than: PTCL-NOS, AITL, ALK-ALCL
  3. Stage I
  4. Prior treatment for lymphoma
  5. Positive serologic markers for human immunodeficiency virus (HIV)
  6. Active hepatitis B virus (HBV) infection
  7. Active hepatitis C virus (HCV) infection
  8. Levels of serum bilirubin, alkaline phosphatase and transaminases > 2 the upper normal limit, if not disease related
  9. Ejection fraction < 50% and no myocardial stroke in the last year or QT prolongation (QTc interval > 480 msec using the Fridericia formula)
  10. Clearance of creatinine < 60 ml/min if not disease related
  11. Spirometry Diffusion Capacity (DLCO) < 50%
  12. Pregnancy or lactation
  13. Patient not agreeing to take adequate contraceptive measures during the study
  14. Psychiatric disease that precludes understanding concepts of the trial or signing informed consent
  15. Any active, uncontrolled infection
  16. Prior history of malignancies other than PTCLs in the last five years (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02223208


Contacts
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Contact: Uffici Studi FIL 0039 0131033153 segreteria@filinf.it

Locations
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Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
Investigators
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Principal Investigator: Paolo Corradini, Prof Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

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Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT02223208    
Other Study ID Numbers: FIL_PTCL13
First Posted: August 22, 2014    Key Record Dates
Last Update Posted: March 20, 2020
Last Verified: March 2020
Keywords provided by Fondazione Italiana Linfomi ONLUS:
PTCL
PTCL-NOS
AITL
ALCL
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphadenopathy
Prednisone
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Etoposide
Etoposide phosphate
Romidepsin
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists