Overview

This trial is active, not recruiting.

Condition mantle cell lymphoma refractory
Treatments torisel dose 15 mg and r-chop, torisel dose 15 mg and r-fc, torisel dose 15 mg and r-dha, torisel dose 25 mg and r-chop, torisel dose 50 mg and r-chop, torisel dose 75 mg and r-chop, torisel dose 25 mg and r-fc, torisel dose 50 mg and r-fc, torisel dose 75 mg and r-fc, torisel dose 25 mg and r-dha, torisel dose 50 mg and r-dha, torisel 75 mg and r-dha
Phase phase 1/phase 2
Sponsor The Lymphoma Academic Research Organisation
Collaborator French Innovative Leukemia Organisation
Start date November 2011
End date May 2015
Trial size 63 participants
Trial identifier NCT01389427, T³

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 15 mg
torisel dose 15 mg and r-chop Arm A cohort -1
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).
torisel dose 15 mg and r-fc Arm B cohort -1
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).
torisel dose 15 mg and r-dha Arm C cohort -1
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).
(Experimental)
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 25 mg
torisel dose 25 mg and r-chop Arm A cohort 1
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).
torisel dose 25 mg and r-fc Arm B cohort 1
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).
torisel dose 25 mg and r-dha Arm C cohort 1
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).
(Experimental)
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 50 mg
torisel dose 50 mg and r-chop Arm A cohort 2
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).
torisel dose 50 mg and r-fc Arm B cohort 2
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).
torisel dose 50 mg and r-dha Arm C cohort 2
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).
(Experimental)
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 75 mg
torisel dose 75 mg and r-chop Arm A cohort 3
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).
torisel dose 75 mg and r-fc Arm B cohort 3
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).
torisel 75 mg and r-dha Arm C cohort 3
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).

Primary Outcomes

Measure
Incidence of Dose Limiting Toxicities (DLT)
time frame: 56 days

Secondary Outcomes

Measure
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
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
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
Overall Response at the end of treatment
time frame: 28 days up to 42 days after the last treatment dose
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
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

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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
Principal investigator Steven LE GOUILL, Professor
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by The Lymphoma Academic Research Organisation.