STORM: Temsirolimus, Rituximab and DHAP for Relapsed and Refractory Diffuse Large B-cell Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University Hospital Heidelberg
Sponsor:
Collaborators:
Johannes Gutenberg University Mainz
Technische Universität München
Ludwig-Maximilians - University of Munich
University Hospital Ulm
University Hospital Erlangen
Charite University, Berlin, Germany
University Hospital Freiburg
Johann Wolfgang Goethe University Hospitals
Information provided by (Responsible Party):
Mathias Witzens-Harig, University Hospital Heidelberg
ClinicalTrials.gov Identifier:
NCT01653067
First received: July 17, 2012
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Diffuse Large B-Cell Lymphoma
Drug: Rituximab, Temsirolimus, DHAP, intravenous
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital Heidelberg:

Primary Outcome Measures:
  • Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone) [ Time Frame: 09-2012 to 06-2018 (up to six years) ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone) [ Time Frame: 09-2012 to 06-2018 (up to six years) ] [ Designated as safety issue: Yes ]
    In the part I (dose escalation of Temsirolimus) secondary objective is to prove ability to mobilize stem cells in patients scheduled to high dose therapy.

  • Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone) [ Time Frame: 09-2012 to 06-2018 (up to six years) ] [ Designated as safety issue: Yes ]
    In the part II (full target dose) the secondary objective is to evaluate Progression Free Survival

  • Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone) [ Time Frame: 09-2012 to 06-2018 (up to six years) ] [ Designated as safety issue: Yes ]
    In the part II (full target dose) the secondary objective is to evaluate Overall Survival

  • Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone) [ Time Frame: 09-2012 to 06-2018 (up to six years) ] [ Designated as safety issue: Yes ]
    In the part II (full target dose) the secondary objective is to evaluate Toxicity


Estimated Enrollment: 88
Study Start Date: September 2012
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab, Temsirolimus, DHAP, intravenous

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 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.

Drug: Rituximab, Temsirolimus, DHAP, intravenous
Maximum tolerated dose of Temsirolimus Rituximab (375 mg/m²) Dexamethasone (120 mg) Cisplatin (100mg/m²) Cytarabine (2x2g/m²))
Other Names:
  • Temsirolimus-R-DHAP
  • Torisel
  • MabThera
  • Fortecortin
  • ARA-C
  • ARA-cell
  • Depocyte
  • R-DHAP
  • Rituximab-DHAP
  • Temsirolimus,Rituximab,Dexamethasone,Cisplatine,Cytarabine
  • Temsirolimus-Rituximab-DHAP

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653067

Contacts
Contact: Mathias Witzens-Harig, MD 0049 6221 56 8199 mathias.witzens-harig@med.uni-heidelberg.de

Locations
Germany
University Hospital Freiburg Recruiting
Freiburg, Baden-Württemberg, Germany, 79106
Contact: Gerald Illerhaus, MD    0049-761-27037850      
Principal Investigator: Gerald Illerhaus, MD         
University of Heidelberg Hospital Recruiting
Heidelberg, Baden-Württemberg, Germany, 69120
Contact: Mathias Witzens-Harig, MD    +49 6221 568008    mathias.witzens-harig@med.uni-heidelberg.de   
Principal Investigator: Mathias Witzens-Harig, MD         
University Hospital Ulm Recruiting
Ulm, Baden-Württemberg, Germany, 89081
Contact: Andreas Viardot, MD    0049-731-50045539      
Principal Investigator: Andreas Viardot, MD         
University Hospital Erlangen Recruiting
Erlangen, Bayern, Germany, 91054
Contact: Stefan W. Krause, Prof.    0049-9131-8535957      
Principal Investigator: Stefan W. Krause, Prof.         
Technische Universität München Recruiting
Munich, Bayern, Germany, 81675
Contact: Ulrich Keller, MD    0049-89-41407435      
Principal Investigator: Ulrich Keller, MD         
Ludwig-Maximilians-University of Munich Recruiting
Munich, Bayern, Germany, 81377
Contact: Martin Dreyling, Prof.    0049-89-70952202      
Principal Investigator: Martin Dreyling, Prof.         
Johann Wolfgang Goethe University Hospitals, Frankfurt Not yet recruiting
Frankfurt, Hessen, Germany, 60590
Contact: Johannes Atta, MD         
Principal Investigator: Johannes Atta, MD         
Johannes Guttenberg University Mainz Recruiting
Mainz, Rheinland-Pfalz, Germany, 55101
Contact: Georg Heß, MD    0049-6131-175040      
Principal Investigator: Georg Heß, MD         
Charité University Berlin Recruiting
Berlin, Germany, 12200
Contact: Agnieszka Korfel, MD    0049-30-84452337      
Principal Investigator: Agnieszka Korfel, MD         
Sponsors and Collaborators
Mathias Witzens-Harig
Johannes Gutenberg University Mainz
Technische Universität München
Ludwig-Maximilians - University of Munich
University Hospital Ulm
University Hospital Erlangen
Charite University, Berlin, Germany
University Hospital Freiburg
Johann Wolfgang Goethe University Hospitals
Investigators
Principal Investigator: Mathias Witzens-Harig, MD University Hospital of Heidelberg, Department 5 Hematology, Oncology, Rheumatology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
  More Information

No publications provided by University Hospital Heidelberg

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mathias Witzens-Harig, PD Dr. med. Mathias Witzens-Harig, University Hospital Heidelberg
ClinicalTrials.gov Identifier: NCT01653067     History of Changes
Other Study ID Numbers: STORM-2011, 2011-001491-20
Study First Received: July 17, 2012
Last Updated: August 19, 2013
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Heidelberg:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Sirolimus
Everolimus
Rituximab
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 20, 2014