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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Mantle Cell Lymphoma Refractory

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Trial Information

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 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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of Dose Limiting Toxicities (DLT)

Outcome Description:

The evaluable for DLT population is the subset of patients from all treated population with a DLT assessment at the two first cycles.

Outcome Time Frame:

56 days

Safety Issue:

Yes

Principal Investigator

Steven LE GOUILL, Professor

Investigator Role:

Principal Investigator

Authority:

France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:

NCT ID:

NCT01389427

Start Date:

November 2011

Completion Date:

April 2014

Related Keywords:

  • Mantle Cell Lymphoma Refractory
  • Lymphoma
  • Lymphoma, Mantle-Cell

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