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

Primary Purpose

Diffuse Large B-Cell Lymphoma

Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Rituximab, Temsirolimus, DHAP, intravenous
Sponsored by
Mathias Witzens-Harig
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospital Freiburg
  • University of Heidelberg Hospital
  • University Hospital Ulm
  • University Hospital Erlangen
  • Ludwig-Maximilians-University of Munich
  • Technische Universität München
  • Johann Wolfgang Goethe University Hospitals, Frankfurt
  • Johannes Guttenberg University Mainz
  • Charité University Berlin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab, Temsirolimus, DHAP, intravenous

Arm 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 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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) 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)
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)
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)
In the part II (full target dose) the secondary objective is to evaluate Toxicity

Full Information

First Posted
July 17, 2012
Last Updated
October 26, 2016
Sponsor
Mathias Witzens-Harig
Collaborators
Johannes Gutenberg University Mainz, Technical University of Munich, Ludwig-Maximilians - University of Munich, University Hospital Ulm, University Hospital Erlangen, Charite University, Berlin, Germany, University Hospital Freiburg, Johann Wolfgang Goethe University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01653067
Brief Title
STORM: Temsirolimus, Rituximab and DHAP for Relapsed and Refractory Diffuse Large B-cell Lymphoma
Acronym
STORM
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

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Unknown status
Study Start Date
September 2012 (undefined)
Primary Completion Date
June 2018 (Anticipated)
Study Completion Date
July 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Mathias Witzens-Harig
Collaborators
Johannes Gutenberg University Mainz, Technical University of Munich, Ludwig-Maximilians - University of Munich, University Hospital Ulm, University Hospital Erlangen, Charite University, Berlin, Germany, University Hospital Freiburg, Johann Wolfgang Goethe University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
88 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rituximab, Temsirolimus, DHAP, intravenous
Arm Type
Experimental
Arm 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 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.
Intervention Type
Drug
Intervention Name(s)
Rituximab, Temsirolimus, DHAP, intravenous
Other Intervention Name(s)
Temsirolimus-R-DHAP, Torisel, MabThera, Fortecortin, ARA-C, ARA-cell, Depocyte, R-DHAP, Rituximab-DHAP, Temsirolimus,Rituximab,Dexamethasone,Cisplatine,Cytarabine, Temsirolimus-Rituximab-DHAP
Intervention Description
Maximum tolerated dose of Temsirolimus Rituximab (375 mg/m²) Dexamethasone (120 mg) Cisplatin (100mg/m²) Cytarabine (2x2g/m²))
Primary Outcome Measure Information:
Title
Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
Description
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.
Time Frame
09-2012 to 06-2018 (up to six years)
Secondary Outcome Measure Information:
Title
Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
Description
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.
Time Frame
09-2012 to 06-2018 (up to six years)
Title
Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
Description
In the part II (full target dose) the secondary objective is to evaluate Progression Free Survival
Time Frame
09-2012 to 06-2018 (up to six years)
Title
Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
Description
In the part II (full target dose) the secondary objective is to evaluate Overall Survival
Time Frame
09-2012 to 06-2018 (up to six years)
Title
Safety, Tolerability and Efficacy of a combination therapy of Temsirolimus added to the standard therapy, Rituximab and DHAP (Cytarabine, Cisplatine, Dexamethasone)
Description
In the part II (full target dose) the secondary objective is to evaluate Toxicity
Time Frame
09-2012 to 06-2018 (up to six years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathias Witzens-Harig, MD
Organizational Affiliation
University Hospital of Heidelberg, Department 5 Hematology, Oncology, Rheumatology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Freiburg
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
University of Heidelberg Hospital
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
University Hospital Ulm
City
Ulm
State/Province
Baden-Württemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
University Hospital Erlangen
City
Erlangen
State/Province
Bayern
ZIP/Postal Code
91054
Country
Germany
Facility Name
Ludwig-Maximilians-University of Munich
City
Munich
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
Facility Name
Technische Universität München
City
Munich
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
Johann Wolfgang Goethe University Hospitals, Frankfurt
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Johannes Guttenberg University Mainz
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Charité University Berlin
City
Berlin
ZIP/Postal Code
12200
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
23799873
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.
Results Reference
derived

Learn more about this trial

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

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