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

NCT ID: NCT01653067

Last Updated: 2016-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2018-07-31

Brief Summary

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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

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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.

Conditions

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Diffuse Large B-Cell Lymphoma

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Rituximab, Temsirolimus, DHAP, intravenous

Intervention Type DRUG

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

Interventions

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Rituximab, Temsirolimus, DHAP, intravenous

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

Intervention Type DRUG

Other Intervention Names

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

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johannes Gutenberg University Mainz

OTHER

Sponsor Role collaborator

Technical University of Munich

OTHER

Sponsor Role collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role collaborator

University Hospital Ulm

OTHER

Sponsor Role collaborator

University Hospital Erlangen

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

University Hospital Freiburg

OTHER

Sponsor Role collaborator

Johann Wolfgang Goethe University Hospital

OTHER

Sponsor Role collaborator

Mathias Witzens-Harig

OTHER

Sponsor Role lead

Responsible Party

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Mathias Witzens-Harig

PD Dr. med. Mathias Witzens-Harig

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Mathias Witzens-Harig, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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University Hospital Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

University of Heidelberg Hospital

Heidelberg, Baden-Wurttemberg, Germany

Site Status

University Hospital Ulm

Ulm, Baden-Wurttemberg, Germany

Site Status

University Hospital Erlangen

Erlangen, Bavaria, Germany

Site Status

Ludwig-Maximilians-University of Munich

Munich, Bavaria, Germany

Site Status

Technische Universität München

Munich, Bavaria, Germany

Site Status

Johann Wolfgang Goethe University Hospitals, Frankfurt

Frankfurt am Main, Hesse, Germany

Site Status

Johannes Guttenberg University Mainz

Mainz, Rhineland-Palatinate, Germany

Site Status

Charité University Berlin

Berlin, State of Berlin, Germany

Site Status

Countries

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Germany

References

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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.

Reference Type DERIVED
PMID: 23799873 (View on PubMed)

Other Identifiers

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2011-001491-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

STORM-2011

Identifier Type: -

Identifier Source: org_study_id