Clinical trial NCT01653067: STORM: Temsirolimus, Rituximab and DHAP for Relapsed and Refractory Diffuse Large B-cell Lymphoma
Official title: A Phase II Trial to Evaluate the Safety, Feasibility and Efficacy of a Salvage Therapy Consisting of Temsirolimus Added to the Standard Therapy R-DHAP for the Treatment of Patients With Relapsed or Refractory DLBCL - the STORM Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: Non Hodgkin´s Lymphoma
Diffuse Large B-Cell Lymphoma
Aggressive Lymphoma
Aggressive Non Hodgkin´s Lymphoma
NHL
aNHL
Temsirolimus
Torisel
Relapsed Non Hodgkin´s Lymphoma
Relapsed Diffuse Large B-Cell Lymphoma
aggressive NHL
B-NHL
aggressive B-NHL
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: Johannes Gutenberg University Mainz
name: Technical University of Munich
name: Ludwig-Maximilians - University of Munich
name: University Hospital Ulm
name: University Hospital Erlangen
name: Charite University, Berlin, Germany
name: University Hospital Freiburg
name: Johann Wolfgang Goethe University Hospital
First posted: 2012-07-30
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The STORM-trial consists of two parts. In the part I (dose escalation of Temsirolimus) the primary objective is to establish a maximum tolerated dose of Temsirolimus in combination with Rituximab and DHAP. Secondary objective is to prove ability to mobilize stem cells in patients scheduled to high dose therapy.

In the part II (full target dose) the primary objective is to evaluate the ORR in patients with relapsed diffuse large B cell lymphoma (DLBCL). The secondary objective is to evaluate progression free survival (PFS), overall survival (OS) and Toxicity.

Detailed description: This is a multicenter, open label, single arm, phase II study. There will be no placebo usage within this trial. In the part I, dose escalation part, of this trial 6 patients will be included in each dose level. There will be 4 cohorts, administering up to a maximum of 4 cycles 25 mg, 50 mg, 75mg or 100mg Temsirolimus in combination with Rituximab and DHAP.

Treatment regimen part I:

Part I - Cohort A, B, C, D, X Temsirolimus 25 (A), 50 (B), 75 (C),100 (D) or 15 (X) mg, Day 1, 8, Rituximab (375 mg/m² day 2) Dexamethasone 40mg day 3-6 Cisplatine 100 mg/m² day 3 Cytarabine 2x2 g/m² day 4

...repeat day 22, up to a maximum of 4 cycles In part I, after inclusion of 6 patients, each patient has to receive at least 1 complete cycle w/o dose limiting toxicity until the enrollment into the next cohort can be initiated.

In the part II of the trial 40 patients will be included to receive the full target dose, established within the part I of the study.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically proven diagnosis of diffuse large cell B-cell lymphoma (DLBCL) according to the World Health Organization classification.
* Documented relapse or progression following at least one treatment but a maximum of 2 prior treatments. Prior treatment must have included at least 3 cycles of anthracycline containing chemotherapy (e.g. CHOP-like)
* Any of the following: at least 1 measurable tumor mass (\>1.5 cm x \>1.0 cm), involvement of any organ or bone marrow infiltration
* Subjects 18 years or older
* Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
* Adequate bone marrow reserve: Platelets of at least 75000/µl, absolute neutrophil count at least 1500/µl
* Alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) \< 2.5 x ULN, Total bilirubin \< 1.5 x ULN
* Calculated creatinine clearance (MDRD) \> 70 mL/min
* Eastern Cooperative Oncology Group \[ECOG\] performance Status \< 3
* Female subject must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum ß-hCG pregnancy test at screening

Exclusion Criteria:

* Active central nervous System lymphoma. Brain MRI is required only if clinically indicated
* Pregnancy or breast feeding women
* Lymphoma other than DLBCL
* Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinemia)
* Active uncontrolled infections including HIV-positivity, active Hep B or C
* Mental status precluding patient's compliance
* Prior treatment with Temsirolimus
* Known CD20 negativity
* Patients refractory to DHAP in a prior treatment line
* Prior autologous or allogeneic stem cell or bone marrow transplantation
* Peripheral neuropathy or neuropathic pain of Grade 2 or worse
* Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, DCIS of the breast, or other solid tumors curatively treated with no evidence of disease for \>5 years
* Concurrent treatment with another investigational agent during the conduct of the trial.
* Concurrent participation in non-treatment studies is not excluded
* Known intolerance to Sirolimus or derivates, Cytarabine, Cisplatine or Rituximab.

Primary outcomes:
measure: Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
timeFrame: 09-2012 to 06-2018 (up to six years)
Secondary outcomes:
measure: Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
timeFrame: 09-2012 to 06-2018 (up to six years)
measure: Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
timeFrame: 09-2012 to 06-2018 (up to six years)
measure: Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
timeFrame: 09-2012 to 06-2018 (up to six years)
measure: Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
timeFrame: 09-2012 to 06-2018 (up to six years)
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: University Hospital Freiburg
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: University of Heidelberg Hospital
state: Baden-Württemberg
city: Ulm
country: Germany
facility: University Hospital Ulm
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: University Hospital Erlangen
state: Bayern
city: Munich
country: Germany
facility: Ludwig-Maximilians-University of Munich
state: Bayern
city: Munich
country: Germany
facility: Technische Universität München
state: Bayern
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe University Hospitals, Frankfurt
state: Hessen
city: Mainz
country: Germany
facility: Johannes Guttenberg University Mainz
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Charité University Berlin
Study officials:
affiliation: University Hospital of Heidelberg, Department 5 Hematology, Oncology, Rheumatology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
name: Mathias Witzens-Harig, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Witzens-Harig M, Memmer ML, Dreyling M, Hess G. A phase I/II trial to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor Temsirolimus added to standard therapy of Rituximab and DHAP for the treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma - the STORM trial. BMC Cancer. 2013 Jun 25;13:308. doi: 10.1186/1471-2407-13-308.