Escalating Doses of Torisel in Combination With Three Chemotherapies Regimens: R-CHOP, R-FC or R-DHA for Patients With Relapsed/Refractory Mantle Cell Lymphoma (MCL). (T³)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by The Lymphoma Academic Research Organisation
Sponsor:
Collaborator:
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT01389427
First received: July 4, 2011
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

This is a multicenter, open label, three arms, Phase IB study.

A dose escalation phase of Temsirolimus (Torisel™) administered in intravenous (IV) at day 2, day 8 and day 15 in combination with three chemotherapies regimens for patients in relapsed/refractory Mantle Cell Lymphoma (MCL):

  • Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (R-CHOP) administered every 3 weeks for 6 cycles,
  • Rituximab-Fludarabine-Cyclophosphamide (R-FC) administered every 4 weeks for 6 cycles,
  • Rituximab-Aracytine high dose-Dexamethasone (R-DHA) administered every 4 weeks for 6 cycles.

Condition Intervention Phase
Mantle Cell Lymphoma Refractory
Drug: Torisel and R-CHOP
Drug: Torisel and R-FC
Drug: Torisel and R-DHA
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 Multicenter Phase IB Dose Escalation Study to Evaluate the Safety, Feasibility and Efficacy of the Torisel-Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (T-R-CHOP), Torisel-Rituximab-Fludarabine-Cyclophosphamide (T-R-FC) and Torisel-Rituximab-Aracytine High Dose-Dexamethasone (T-R-DHA) for the Treatment of Patients in Relapsed/Refractory Mantle Cell Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities (DLT) [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
    The evaluable for DLT population is the subset of patients from all treated population with a DLT assessment at the two first cycles.


Secondary Outcome Measures:
  • Complete Response Rate(CR) after 4 cycles and at the end of treatment [ Time Frame: 28 days up to 42 days after the last treatment dose ] [ Designated as safety issue: No ]
    Response at the end of treatment will be assessed after four cycles and at the end of complete treatment if the patient received all planned cycles or at withdrawal. Patients without response assessments (due to whatever reason) will be considered non-responders. A descriptive analysis will also be performed considering as non-responders all patients who relapsed or died during the treatment phase even if they were prematurely withdrawn as responders.

  • 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 up to 3 years ] [ Designated as safety issue: No ]
    Progression-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse or death from any cause, according to the Cheson 2007 criteria. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.

  • 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 up to 3 years ] [ Designated as safety issue: No ]
    Duration of response will be measured from the date of first documentation of a response (CR or PR at the end of treatment) to the date of first documented evidence of progression/relapse or death from any cause, according to the Cheson 2007 criteria. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.

  • Overall Response at the end of treatment [ Time Frame: 28 days up to 42 days after the last treatment dose ] [ Designated as safety issue: No ]
    The same disease response assessment used for complete response rate will be considered to determine the Overall Response Rate. A Patient will be defined as a responder if he/she has a complete response (CR/CRu) or partial response (PR) after four cycles and at the end of treatment. A descriptive analysis will also be performed considering as non-responders all patients who relapsed or died during treatment phase even if they were prematurely withdrawn as responders.

  • Overall Survival (OS) [ Time Frame: From the date of inclusion to the date of first documentated disease progression, relapse or death from any cause up to 3 years ] [ Designated as safety issue: No ]
    Overall survival will be measured from the date of inclusion to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of the last contact.

  • Safety of association Temsirolimus with the three chemotherapy regimens [ Time Frame: From the date of informed consent signature to 28 days after the last drug administration ] [ Designated as safety issue: Yes ]

    All subjects who received at least one dose of Temsirolimus (Torisel™) will be considered evaluable and will be included in the safety analysis.

    Analysis of safety will be performed by summarizing adverse events, laboratory data, vital signs and ECOG per-formance status. When applicable, a summary of safety data will also be performed by cycle.



Estimated Enrollment: 63
Study Start Date: November 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Torisel dose 15mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 15 mg
Drug: Torisel and R-CHOP
Torisel in association with Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (R-CHOP) administered every 3 weeks (21 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm A cohort -1
Drug: Torisel and R-FC
Torisel in association with Rituximab-Fludarabine-Cyclophosphamide (R-FC) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm B cohort -1
Drug: Torisel and R-DHA
Torisel in association with Rituximab-Aracytine (high dose)-Dexamethasone (R-DHA) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm C cohort -1
Experimental: Torisel dose 25mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 25 mg
Drug: Torisel and R-CHOP
Torisel in association with Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (R-CHOP) administered every 3 weeks (21 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm A cohort 1
Drug: Torisel and R-FC
Torisel in association with Rituximab-Fludarabine-Cyclophosphamide (R-FC) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm B cohort 1
Drug: Torisel and R-DHA
Torisel in association with Rituximab-Aracytine (high dose)-Dexamethasone (R-DHA) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm C cohort 1
Experimental: Torisel dose 50mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 50 mg
Drug: Torisel and R-CHOP
Torisel in association with Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (R-CHOP) administered every 3 weeks (21 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm A cohort 2
Drug: Torisel and R-FC
Torisel in association with Rituximab-Fludarabine-Cyclophosphamide (R-FC) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm B cohort 2
Drug: Torisel and R-DHA
Torisel in association with Rituximab-Aracytine (high dose)-Dexamethasone (R-DHA) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm C cohort 2
Experimental: Torisel dose 75mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 75 mg
Drug: Torisel and R-CHOP
Torisel in association with Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (R-CHOP) administered every 3 weeks (21 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm A cohort 3
Drug: Torisel and R-FC
Torisel in association with Rituximab-Fludarabine-Cyclophosphamide (R-FC) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm B cohort 3
Drug: Torisel and R-DHA
Torisel in association with Rituximab-Aracytine (high dose)-Dexamethasone (R-DHA) administered every 4 weeks (28 days) for 6 cycles for patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Other Name: Arm C cohort 3

Detailed Description:

This is a three arms trial that investigates Temsirolimus (Torisel™) in combination with three chemotherapy regimens (R-CHOP, R-FC or R-DHA).

Primary Objective:

- To assess the feasibility of these three chemotherapy regimens in combination with Temsirolimus (Torisel™) and to assess the incidence of dose limiting toxicities (DLT) during the two first cycles of Temsirolimus (Torisel™) in combination with three chemotherapy regimens in order to determine the maximal tolerate dose (MTD) in a dose escalating study design in a population of patients in relapsed/refractory Mantle Cell Lymphoma (MCL).

Secondary objectives:

  • To assess the safety of the association Temsirolimus with the three chemotherapy regimens,
  • To determine the efficacy of the association of Temsirolimus (Torisel™) and these three chemotherapy regimens after 4 cycles and after 6 cycles at the end of treatment: response rate and complete response rate (CR), progression-free survival (PFS), response duration (RD) and overall survival (OS).

All subjects who received at least one dose of Temsirolimus (Torisel™) will be considered evaluable and will be included in the safety analysis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically or cytologically confirmed refractory or relapsed Mantle Cell Lymphoma (at initial diagnosis or relapse),
  2. Ann Arbor Stage I-IV with at least one tumor site measurable,
  3. Patients who received prior therapy (at least one but no more than three lines therapies) for Mantle Cell Lymphoma (MCL),
  4. Aged ≥ 18 years,
  5. ECOG performance status 0, 1 or 2,
  6. Adequate hepatic and renal function :

    • Serum Glutamic Oxaloacetic Transaminase (SGOT)/AST or Serum Glutamic Pyruvic TransaminaseSGPT/ALT ≤ 3.0 x upper limit of normal (ULN),
    • Serum Total Bilirubin ≤ 1.5 mg/dL (26 μmol/L) except in case of hemolytic anemia,
    • Serum Creatinine ≤ 2 mg/dL (177 μmol/L) or calculated Creatinine Clearance (Cock-croft-Gault formula) of ≥ 50 mL /min
  7. Adequate bone marrow reserve :

    • Absolute neutrophil count (ANC) ≥ 1 G/L (1,000 cells/mm³)
    • Platelets count ≥ 50 G/L
    • Hemoglobin ≥ 9.0 g/dL,
  8. Signed and date informed consent,
  9. Life expectancy of ≥ 90 days (3 months)

Exclusion Criteria:

  1. Other types of lymphomas, e.g. B-cell lymphoma,
  2. Contraindication to any drug contained in the three chemotherapy regimens (R-CHOP, R-FC, R-DHA),
  3. Tested positive for HIV,
  4. Active Hepatitis B and/or C,
  5. Exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited, to active systemic fungal infection, diagnosis of fever and neutropenia,
  6. Any serious active disease or co-morbid medical condition (according to investigator's decision),
  7. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form,
  8. Received a biological agent for anti-neoplastic intent within 30 days prior to the first dose of study drug,
  9. Use of any standard or experimental anti-cancer drug therapy within 30 days prior to the first dose of study drug,
  10. 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,
  11. Left Ventricular Ejection Fraction < 45% (calculated by echocardiographic or scintigraphic method),
  12. Pregnancy or breast feeding women,
  13. Women of childbearing potential who not willing to use an adequate method of birth controls for the duration of the study and for twelve months after the end of treatment,
  14. Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for twelve months after the end of treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01389427

Contacts
Contact: Anastassia TRAORE 04 72 66 93 33
Contact: Sabine BALOUET 04 72 66 93 33

Locations
France
CHU de Grenoble MICHALLON Recruiting
Grenoble Cedex 9, Hôpital Nord 217, France, 38043
Contact: Rémy GRESSIN, Professor    04 76 76 59 53    rgressin@chu-grenoble.fr   
Principal Investigator: Rémy GRESSIN, Professor         
Sub-Investigator: Claude-Eric BULABOIS, Doctor         
Sub-Investigator: Stéphane COURBY, Doctor         
Sub-Investigator: Lysiane MOLINA, Doctor         
Sub-Investigator: Brigitte PEGOURIE-BANDELIER, Doctor         
Sub-Investigator: Anne THIEBAUT, Doctor         
Hôtel Dieu - Université de Nantes Recruiting
Nantes cedex, Place Alexis Ricordeau, France, 44093
Contact: Steven LE GOUILL, Professor    02 40 08 32 71    steven.legouill@chu-nantes.fr   
Principal Investigator: Steven Le GOUILL, Professor         
Sub-Investigator: Nicolas BLIN, Doctor         
Sub-Investigator: Aline CLAVERT, Doctor         
Sub-Investigator: Viviane DUBRUILLE, Doctor         
Sub-Investigator: Thomas GASTININE, Doctor         
Sub-Investigator: Béatrice MAHE, Doctor         
Sub-Investigator: Philipee MOREAU, Doctor         
Sub-Investigator: Virginie ROLAND, Doctor         
Hôpital Henri Mondor Recruiting
Creteil, France, 94010
Contact: Corinne HAIOUN, Professor    01 49 81 41 54    corinne.haioun@hmn.aphp.fr   
Principal Investigator: Corinne HAIOUN, Professor         
Sub-Investigator: Karim BELHADJ-MERZOUG, Doctor         
Sub-Investigator: Jehan DUPUIS, Doctor         
Sub-Investigator: Isabelle GAILLARD, Doctor         
Sub-Investigator: Violaine SAFAR, Doctor         
CHU de Dijon Recruiting
Dijon, France, 21000
Contact: Olivier CASASNOVAS, Professor    03 80 29 30 31    olivier.casasnovas@chu-dijon.fr   
Principal Investigator: Olivier CASASNOVAS, Professor         
Hôpital Saint-Eloi Recruiting
Montpellier, France, 34295
Contact: Guillaume CARTRON, Professor    04 67 33 80 79    g-cartron@chu-montpellier.fr   
Principal Investigator: Guillaume CARTRON, Professor         
Sub-Investigator: Robert NAVARRO, Doctor         
Sub-Investigator: Philippe QUITTET, Doctor         
Sub-Investigator: Gaëlle OLIVIER, Doctor         
Sub-Investigator: Jean-François ROSSI, Doctor         
Hôpital Necker Recruiting
Paris, France, 75743
Contact: Richard DELARUE, Doctor    01 44 49 52 97    richard.delarue@nck.ap-hop-paris.fr   
Principal Investigator: Richard DELARUE, Doctor         
Sub-Investigator: Olivier HERMINE, Doctor         
Hôpital Saint Louis Recruiting
Paris, France, 75475
Contact: Catherine THIEBLEMONT, Professor    01 42 49 92 36    catherine.thieblemont@sls.aphp.fr   
Principal Investigator: Catherine THIEBLEMONT, Professor         
Sub-Investigator: Pauline BRICE, Doctor         
Sub-Investigator: Bénédicte DEAU-FISCHER, Doctor         
Sub-Investigator: Patricia FRANCHI-REZGUI, Doctor         
Sub-Investigator: Jean-Marc ZINI, Doctor         
Groupe hospitalier Sud Hôpital Haut-Lévêque Recruiting
Pessac, France, 33604
Contact: Kamal BOUABDALLAH    05 57 65 65 11    krimo.bouabdallah@chu-bordeaux.fr   
Principal Investigator: Kamal BOUABDALLAH, Doctor         
Sub-Investigator: Noël MILPIED, Doctor         
Sub-Investigator: Cédric DUCLOS, Doctor         
Sub-Investigator: Marie-Sarah DILHUYDY, Doctor         
Centre Hospitalier Lyon Sud Recruiting
Pierre Benite, France, 69310
Contact: Bertrand COIFFIER, Professor    04 78 86 43 08    bertrand.coiffier@chu-lyon.fr   
Principal Investigator: Bertrand COIFFIER, Professor         
Sub-Investigator: Gilles SALLES, Professor         
Sub-Investigator: Fadhela BOUAFIA-SAUVY, Doctor         
Sub-Investigator: Marie BOUTELOUP, Doctor         
Sub-Investigator: Sophie DUPIRE, Doctor         
Sub-Investigator: Daniel ESPINOUSE, Doctor         
Sub-Investigator: Lionel KARLIN, Doctor         
Sub-Investigator: Anne-Sophie MICHALLET, Doctor         
Sub-Investigator: Catherine TRAULLE, Doctor         
CHU Pontchaillou Recruiting
Rennes, France, 35003
Contact: Thierry LAMY, Doctor    02 99 28 42 91    thierry.lamy.de.la.chapelle@chu-rennes.fr   
Principal Investigator: Thierry LAMY, Professor         
Sub-Investigator: Marc BERNARD, Doctor         
Sub-Investigator: Xavier CAHU, Doctor         
Sub-Investigator: Charles DAURIAC, Doctor         
Sub-Investigator: Sophie DE GUIBERT, Doctor         
Sub-Investigator: Martine ESCOFFRE, Doctor         
Sub-Investigator: Roch HOUOT, Doctor         
Sub-Investigator: Stanislas NIMUBONA, Doctor         
CHU de Tours - Hôpital Bretonneau Recruiting
Tours, France, 37000
Contact: Emmanuel GYAN, MCU-PH    +33 2 47 47 37 12    emmanuel.gyan@univ-tours.fr   
Principal Investigator: Emmanuel Gyan, MCU-PH         
Institut Gustave Roussy Withdrawn
Villejuif, France, 94805
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Investigators
Principal Investigator: Steven LE GOUILL, Professor
  More Information

No publications provided

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT01389427     History of Changes
Other Study ID Numbers:
Study First Received: July 4, 2011
Last Updated: September 23, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Sirolimus
Everolimus
Rituximab
Fludarabine
Dexamethasone
Vincristine
Doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics

ClinicalTrials.gov processed this record on October 19, 2014