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).

NCT01389427 | Completed Phase 1 DMC

• 1 other identifier: T³
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Mantle Cell Lymphoma Refractory

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicities (DLT)

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

  56 days

Secondary Outcomes (6)

• Complete Response Rate(CR) after 4 cycles and at the end of treatment

  28 days up to 42 days after the last treatment dose

• Progression-free survival (PFS)

  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

  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

  28 days up to 42 days after the last treatment dose

• Overall Survival (OS)

  From the date of inclusion to the date of first documentated disease progression, relapse or death from any cause up to 3 years

Study Arms (4)

Torisel 15 mg

EXPERIMENTAL

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

Drug: Torisel dose 15 mg and R-CHOP; Drug: Torisel dose 15 mg and R-FC; Drug: Torisel dose 15 mg and R-DHA

Torisel 25 mg

EXPERIMENTAL

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

Drug: Torisel dose 25 mg and R-CHOP; Drug: Torisel dose 25 mg and R-FC; Drug: Torisel dose 25 mg and R-DHA

Torisel 50 mg

EXPERIMENTAL

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

Drug: Torisel dose 50 mg and R-CHOP; Drug: Torisel dose 50 mg and R-FC; Drug: Torisel dose 50 mg and R-DHA

Torisel 75 mg

EXPERIMENTAL

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

Drug: Torisel dose 75 mg and R-CHOP; Drug: Torisel dose 75 mg and R-FC; Drug: Torisel 75 mg and R-DHA

Interventions

Torisel dose 15 mg and R-CHOP 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).

Also known as: Arm A cohort -1

Torisel 15 mg

Torisel dose 15 mg and R-FC 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).

Also known as: Arm B cohort -1

Torisel 15 mg

Torisel dose 15 mg and R-DHA 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).

Also known as: Arm C cohort -1

Torisel 15 mg

Torisel dose 25 mg and R-CHOP 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).

Also known as: Arm A cohort 1

Torisel 25 mg

Torisel dose 50 mg and R-CHOP 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).

Also known as: Arm A cohort 2

Torisel 50 mg

Torisel dose 75 mg and R-CHOP 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).

Also known as: Arm A cohort 3

Torisel 75 mg

Torisel dose 25 mg and R-FC 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).

Also known as: Arm B cohort 1

Torisel 25 mg

Torisel dose 50 mg and R-FC 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).

Also known as: Arm B cohort 2

Torisel 50 mg

Torisel dose 75 mg and R-FC 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).

Also known as: Arm B cohort 3

Torisel 75 mg

Torisel dose 25 mg and R-DHA 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).

Also known as: Arm C cohort 1

Torisel 25 mg

Torisel dose 50 mg and R-DHA 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).

Also known as: Arm C cohort 2

Torisel 50 mg

Torisel 75 mg and R-DHA 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).

Also known as: Arm C cohort 3

Torisel 75 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically confirmed refractory or relapsed Mantle Cell Lymphoma (at initial diagnosis or relapse),
• Ann Arbor Stage I-IV with at least one tumor site measurable,
• Patients who received prior therapy (at least one but no more than three lines therapies) for Mantle Cell Lymphoma (MCL),
• Aged ≥ 18 years,
• ECOG performance status 0, 1 or 2,
• 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
• 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,
• Signed and date informed consent,
• Life expectancy of ≥ 90 days (3 months)

You may not qualify if:

• Other types of lymphomas, e.g. B-cell lymphoma,
• Contraindication to any drug contained in the three chemotherapy regimens (R-CHOP, R-FC, R-DHA),
• Tested positive for HIV,
• Active Hepatitis B and/or C,
• Exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited, to active systemic fungal infection, diagnosis of fever and neutropenia,
• Any serious active disease or co-morbid medical condition (according to investigator's decision),
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form,
• Received a biological agent for anti-neoplastic intent within 30 days prior to the first dose of study drug,
• Use of any standard or experimental anti-cancer drug therapy within 30 days prior to the first dose of study drug,
• 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,
• Left Ventricular Ejection Fraction \< 45% (calculated by echocardiographic or scintigraphic method),
• Pregnancy or breast feeding women,
• 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,
• 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.

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• French Innovative Leukemia Organisation: collaborator

Study Sites (11)

CHU de Grenoble MICHALLON

Grenoble, Hôpital Nord 217, 38043, France

Location

Hôtel Dieu - Université de Nantes

Nantes, Place Alexis Ricordeau, 44093, France

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon

Dijon, 21000, France

Location

Hôpital Saint-Eloi

Montpellier, 34295, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

Hôpital Necker

Paris, 75743, France

Location

Groupe hospitalier Sud Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

CHU Pontchaillou

Rennes, 35003, France

Location

CHU de Tours - Hôpital Bretonneau

Tours, 37000, France

Location

MeSH Terms

Interventions

temsirolimus

Study Officials

• Steven LE GOUILL, Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2011
• First Posted: July 8, 2011
• Study Start: November 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: September 1, 2015
• Last Updated: March 9, 2017

Record last verified: 2017-03

Locations

FR (11)