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).

NCT ID: NCT01389427

Last Updated: 2017-03-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2015-09-30

Brief Summary

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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

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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.

Conditions

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Mantle Cell Lymphoma Refractory

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Torisel 15 mg

Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 15 mg

Group Type EXPERIMENTAL

Torisel dose 15 mg and R-CHOP

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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).

Torisel 25 mg

Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 25 mg

Group Type EXPERIMENTAL

Torisel dose 25 mg and R-CHOP

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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).

Torisel 50 mg

Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 50 mg

Group Type EXPERIMENTAL

Torisel dose 50 mg and R-CHOP

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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).

Torisel 75 mg

Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 75 mg

Group Type EXPERIMENTAL

Torisel dose 75 mg and R-CHOP

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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).

Interventions

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Torisel dose 15 mg 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).

Intervention Type DRUG

Torisel dose 15 mg 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).

Intervention Type DRUG

Torisel dose 15 mg 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).

Intervention Type DRUG

Torisel dose 25 mg 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).

Intervention Type DRUG

Torisel dose 50 mg 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).

Intervention Type DRUG

Torisel dose 75 mg 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).

Intervention Type DRUG

Torisel dose 25 mg 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).

Intervention Type DRUG

Torisel dose 50 mg 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).

Intervention Type DRUG

Torisel dose 75 mg 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).

Intervention Type DRUG

Torisel dose 25 mg 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).

Intervention Type DRUG

Torisel dose 50 mg 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).

Intervention Type DRUG

Torisel 75 mg 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).

Intervention Type DRUG

Other Intervention Names

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Arm A cohort -1 Arm B cohort -1 Arm C cohort -1 Arm A cohort 1 Arm A cohort 2 Arm A cohort 3 Arm B cohort 1 Arm B cohort 2 Arm B cohort 3 Arm C cohort 1 Arm C cohort 2 Arm C cohort 3

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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French Innovative Leukemia Organisation

OTHER

Sponsor Role collaborator

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Steven LE GOUILL, Professor

Role: PRINCIPAL_INVESTIGATOR

Locations

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CHU de Grenoble MICHALLON

Grenoble, Hôpital Nord 217, France

Site Status

Hôtel Dieu - Université de Nantes

Nantes, Place Alexis Ricordeau, France

Site Status

Hôpital Henri Mondor

Créteil, , France

Site Status

CHU de Dijon

Dijon, , France

Site Status

Hôpital Saint-Eloi

Montpellier, , France

Site Status

Hôpital Saint Louis

Paris, , France

Site Status

Hôpital Necker

Paris, , France

Site Status

Groupe hospitalier Sud Hôpital Haut-Lévêque

Pessac, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

CHU Pontchaillou

Rennes, , France

Site Status

CHU de Tours - Hôpital Bretonneau

Tours, , France

Site Status

Countries

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France

Other Identifiers

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Identifier Type: -

Identifier Source: org_study_id

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