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).
Conditions
Mantle Cell Lymphoma Refractory
Conditions: official terms
Lymphoma - Lymphoma, Mantle-Cell
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Torisel dose 15 mg and R-CHOP Type: Drug
Name: Torisel dose 15 mg and R-FC Type: Drug
Name: Torisel dose 15 mg and R-DHA Type: Drug
Name: Torisel dose 25 mg and R-CHOP Type: Drug
Name: Torisel dose 50 mg and R-CHOP Type: Drug
Name: Torisel dose 75 mg and R-CHOP Type: Drug
Name: Torisel dose 25 mg and R-FC Type: Drug
Name: Torisel dose 50 mg and R-FC Type: Drug
Name: Torisel dose 75 mg and R-FC Type: Drug
Name: Torisel dose 25 mg and R-DHA Type: Drug
Name: Torisel dose 50 mg and R-DHA Type: Drug
Name: Torisel 75 mg and R-DHA Type: Drug
Overall Status
Recruiting
Summary
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.
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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.
Locations
CHU de Grenoble MICHALLON
Grenoble Cedex 9, Hôpital Nord 217, France
Status: Recruiting
Contact: Rémy GRESSIN, Professor - 04 76 76 59 53 - rgressin@chu-grenoble.fr
Hôtel Dieu - Université de Nantes
Nantes cedex, Place Alexis Ricordeau, France
Status: Recruiting
Contact: Steven LE GOUILL, Professor - 02 40 08 32 71 - steven.legouill@chu-nantes.fr
Hôpital Henri Mondor
Creteil, France
Status: Recruiting
Contact: Corinne HAIOUN, Professor - 01 49 81 41 54 - corinne.haioun@hmn.aphp.fr
CHU de Dijon
Dijon, France
Status: Recruiting
Contact: Olivier CASASNOVAS, Professor - 03 80 29 30 31 - olivier.casasnovas@chu-dijon.fr
Hôpital Saint-Eloi
Montpellier, France
Status: Recruiting
Contact: Guillaume CARTRON, Professor - 04 67 33 80 79 - g-cartron@chu-montpellier.fr
Hôpital Necker
Paris, France
Status: Recruiting
Contact: Richard DELARUE, Doctor - 01 44 49 52 97 - richard.delarue@nck.ap-hop-paris.fr
Hôpital Saint Louis
Paris, France
Status: Recruiting
Contact: Catherine THIEBLEMONT, Professor - 01 42 49 92 36 - catherine.thieblemont@sls.aphp.fr
Groupe hospitalier Sud Hôpital Haut-Lévêque
Pessac, France
Status: Recruiting
Contact: Kamal BOUABDALLAH - 05 57 65 65 11 - krimo.bouabdallah@chu-bordeaux.fr
Centre Hospitalier Lyon Sud
Pierre Benite, France
Status: Recruiting
Contact: Bertrand COIFFIER, Professor - 04 78 86 43 08 - bertrand.coiffier@chu-lyon.fr
CHU Pontchaillou
Rennes, France
Status: Recruiting
Contact: Thierry LAMY, Doctor - 02 99 28 42 91 - thierry.lamy.de.la.chapelle@chu-rennes.fr
CHU de Tours - Hôpital Bretonneau
Tours, France
Status: Recruiting
Contact: Emmanuel GYAN, MCU-PH - +33 2 47 47 37 12 - emmanuel.gyan@univ-tours.fr
Institut Gustave Roussy
Villejuif, France
Status: Withdrawn
Start Date
November 2011
Completion Date
October 2016
Sponsors
The Lymphoma Academic Research Organisation
Source
The Lymphoma Academic Research Organisation
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page