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

NCT01653067 | Unknown Phase 2 DMC

• 2 other identifiers: STORM-20112011-001491-20
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 9

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.

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

Outcome Measures

Primary Outcomes (1)

• Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)

  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.

  09-2012 to 06-2018 (up to six years)

Secondary Outcomes (4)

• Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)

  09-2012 to 06-2018 (up to six years)

• Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)

  09-2012 to 06-2018 (up to six years)

• Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)

  09-2012 to 06-2018 (up to six years)

• Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)

  09-2012 to 06-2018 (up to six years)

Study Arms (1)

Rituximab, Temsirolimus, DHAP, intravenous

EXPERIMENTAL

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

Interventions

Rituximab, Temsirolimus, DHAP, intravenous DRUG

Maximum tolerated dose of Temsirolimus Rituximab (375 mg/m²) Dexamethasone (120 mg) Cisplatin (100mg/m²) Cytarabine (2x2g/m²))

Also known as: Temsirolimus-R-DHAP, Torisel, MabThera, Fortecortin, ARA-C, ARA-cell, Depocyte, R-DHAP, Rituximab-DHAP, Temsirolimus,Rituximab,Dexamethasone,Cisplatine,Cytarabine, Temsirolimus-Rituximab-DHAP

Rituximab, Temsirolimus, DHAP, intravenous

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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mathias Witzens-Harig: lead
• Johannes Gutenberg University Mainz: collaborator
• Technical University of Munich: collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• University Hospital Ulm: collaborator
• University Hospital Erlangen: collaborator
• Charite University, Berlin, Germany: collaborator
• University Hospital Freiburg: collaborator
• Johann Wolfgang Goethe University Hospital: collaborator

Study Sites (9)

University Hospital Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

University of Heidelberg Hospital

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University Hospital Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

University Hospital Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Ludwig-Maximilians-University of Munich

Munich, Bavaria, 81377, Germany

Location

Technische Universität München

Munich, Bavaria, 81675, Germany

Location

Johann Wolfgang Goethe University Hospitals, Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Johannes Guttenberg University Mainz

Mainz, Rhineland-Palatinate, 55101, Germany

Location

Charité University Berlin

Berlin, State of Berlin, 12200, Germany

Location

Related Publications (1)

• 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.

  PMID: 23799873 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin

Interventions

Rituximab; temsirolimus; dexamethasone acetate; Cytarabine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mathias Witzens-Harig, MD

  University Hospital of Heidelberg, Department 5 Hematology, Oncology, Rheumatology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PD Dr. med. Mathias Witzens-Harig

Study Record Dates

• First Submitted: July 17, 2012
• First Posted: July 30, 2012
• Study Start: September 1, 2012
• Primary Completion: June 1, 2018
• Study Completion: July 1, 2018
• Last Updated: October 27, 2016

Record last verified: 2016-10

Locations

DE (9)