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 May 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: May 22, 2014
Last verified: May 2014

July 4, 2011
May 22, 2014
November 2011
December 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01389427 on ClinicalTrials.gov Archive Site
  • 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as non-responders all patients who relapsed or died during the treatment phase even if they were prematurely withdrawn as responders.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.

Same as current
Not Provided
Not Provided
 
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).
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Mantle Cell Lymphoma Refractory
  • 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
  • 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-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-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 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 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 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 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 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 3
  • Experimental: Torisel dose 15mg
    Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 15 mg
    Interventions:
    • Drug: Torisel and R-CHOP
    • Drug: Torisel and R-FC
    • Drug: Torisel and R-DHA
  • Experimental: Torisel dose 25mg
    Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 25 mg
    Interventions:
    • Drug: Torisel and R-CHOP
    • Drug: Torisel and R-FC
    • Drug: Torisel and R-DHA
  • Experimental: Torisel dose 50mg
    Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 50 mg
    Interventions:
    • Drug: Torisel and R-CHOP
    • Drug: Torisel and R-FC
    • Drug: Torisel and R-DHA
  • Experimental: Torisel dose 75mg
    Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 75 mg
    Interventions:
    • Drug: Torisel and R-CHOP
    • Drug: Torisel and R-FC
    • Drug: Torisel and R-DHA
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
63
September 2015
December 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Anastassia TRAORE 04 72 66 93 33
Contact: Sabine BALOUET 04 72 66 93 33
France
 
NCT01389427
Yes
The Lymphoma Academic Research Organisation
The Lymphoma Academic Research Organisation
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Principal Investigator: Steven LE GOUILL, Professor
The Lymphoma Academic Research Organisation
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP