Temsirolimus, Rituximab and DHAP for relapsed and refractory diffuse large B-cell lymphoma

Phase 1

• Conditions: Diffuse large B-cell lymphoma with documented relapse or progression following at least one but a maximum of two prior treatments, aged older than 18 years; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004943

• Registration Number: EUCTR2011-001491-20-DE
• Lead Sponsor: Ruprecht-Karls University Heidelberg, Medical Faculty

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-07-05
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 88

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, Hemoglobin of at least 10g/dl
· Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) < 2.5 x ULN
· Total bilirubin < 1.5 x ULN except chronic hepatic conditions leading to bilirubin increase but not interfering therapy, e. g. Gilbert´s Syndrom
· Calculated creatinine clearance (according to CKD-EPI, if possible) > 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
· Male subject, if sexual active and with a sexual partner of childbearing age must be practicing an effective method of contraception throughout the study (e.g. surgical sterilization or double-barrier method. Prescription oral contraceptives,
contraceptive injections, intrauterine device, surgically sterilization or contraceptive patch in female sexual partners)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

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 Dexamethasone, Sirolimus or derivates, Cytarabine, Cisplatine or Rituximab.
Known intolerance to any other ingredients contained in the trial therapy. Known intolerance to pre-treatment or premedication in this trial (e.g. Prednisolone, Allopurinol, H1-Blocker, Paracetamole).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified