High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma

NCT02531841 | Unknown Phase 3 DMC

• 1 other identifier: DRKS00005503
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 2

Brief Summary

In the presently planned multicentre Phase III trial the two therapies will be compared: Patients will be randomized after intensified induction treatment with 4 cycles rituximab, methotrexate, cytarabine and thiotepa (MATRix) between first-line high-dose chemotherapy against conventional consolidating therapy with 2 cycles of conventional chemotherapy with R-DeVIC (rituximab, dexamethasone, etoposide, ifosfamide, carboplatin).

Conditions

Diffuse Large B-cell-lymphoma

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure PFS will be measured by the number of events (PD, relapse or death from any cause) within the treatment arms

  Progression-free survival PFS: Response Assessment III at the end of study treatment (EOT) visit and every imaging diagnostic assessments during follow-up period: during year 1-2: every 3 month

  PFS is defined as the time from randomization until PD or relapse or death from any cause up to 24 months after end of treatment

Secondary Outcomes (6)

• The secondary outcome measure CR will be assessed on day 60 after randomization using the IPCG response criteria

  CR will be determined on day 60 after randomization

• The secondary outcome measure Response duration will be measured by the time from CR, CRu or PR until relapse or PD using the IPCG response criteria

  Time from CR, CRu or PR until relapse or PD up to 24 months after end of treatment

• The secondary outcome OS is measured as time from randomization until death of any cause

  OS is defined as time from randomization until death of any cause up to 24 months after end of treatment

• Number of patients with (Serious) adverse events as assessed by CTCAE v4.0

  All SAEs that occur starting from the first administration of the study medication until day 60 after randomization.

• Number of patients with treatment related toxicity as assessed by CTCAE v4.0

  All toxicities that occur starting from the first administration of the study medication until day 60 after randomization.

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Induction Treatment 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation Treatment 2 cycles of R-DeVIC (every 3 weeks): * Rituximab 375 mg/m²/d i.v. (d0) * Dexamethasone 40 mg/d i.v. (d1-3) * Etoposide 100 mg/m²/d i.v. (d1-3) * Ifosfamide 1500 mg/m²/d i.v. (d1-3) * Carboplatin 300 mg/m² i.v. (d1)

Drug: Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®)

Arm B

ACTIVE COMPARATOR

Induction Treatment 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation Treatment High-dose chemotherapy * Carmustine\* 400 mg/m² i.v. (d-6) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) \*if not available at study site, Busulfan can be administered instead: * Busulfan 3,2 mg/kg/d i.v. (d-8-(-7)) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0)

Drug: Arm B (TEPADINA®-CARMUBRIS®-Busilvex®)

Interventions

Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®) DRUG

Arm A 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation 2 cycles of R-DeVIC (every 3 weeks): * Rituximab 375 mg/m²/d i.v. (d0) * Dexamethasone 40 mg/d i.v. (d1-3) * Etoposide 100 mg/m²/d i.v. (d1-3) * Ifosfamide 1500 mg/m²/d i.v. (d1-3) * Carboplatin 300 mg/m² i.v. (d1)

Also known as: Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®

Arm A

Arm B (TEPADINA®-CARMUBRIS®-Busilvex®) DRUG

4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation High-dose chemotherapy (HDT-ASCT): * Carmustine\* 400 mg/m² i.v. (d-6) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) \* if carmustine is not available at the investigation site, busulfan can be administered instead: * Busulfan 3,2 mg/kg/d (d-8-(-7)) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0)

Also known as: TEPADINA®-CARMUBRIS®-Busilvex®

Arm B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Immunocompetent patients with newly-diagnosed primary central nervous system B-cell lymphoma
• Age 18-65 years irrespective of ECOG or 66-70 years (with ECOG Performance Status ≤2)
• Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist.
• Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
• Disease exclusively located in the CNS
• At least one measurable lesion
• Previously untreated patients (previous or ongoing steroid treatment admitted)
• Sexually active patients of childbearing potential who agree to take adequate contraceptive measures during study participation
• Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease
• ADDITIONAL RANDOMIZATION CRITERIA
• Sufficient stem cell harvest (≥ 5 x 106 CD34+ cells/kg of body weight)
• Complete remission, unconfirmed complete remission or partial remission
• Central pathology results confirming local results

You may not qualify if:

• Congenital or acquired immunodeficiency
• Systemic lymphoma manifestation (outside the CNS)
• Isolated ocular lymphoma without manifestation in the brain parenchyma or spinal cord
• Previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years
• Previous Non-Hodgkin lymphoma at any time
• Inadequate bone marrow (platelet count decreased ≥CTC grade 1, anemia ≥CTC grade 1, neutrophil count decreased ≥CTC grade 1), renal (creatinine clearance \<60 ml/min), cardiac (ejection fraction decreased ≥CTC grade 2), or hepatic function (blood bilirubin increased ≥CTC grade 2, alanine aminotransferase increased ≥CTC grade 2, aspartate aminotransferase increased ≥CTC grade 2 or gamma-GT increased ≥CTC grade 2)
• HBsAg, anti-HBc or HCV positivity
• HIV infection, previous organ transplantation or other clinical evident form of immunodeficiency
• Concurrent treatment with other experimental drugs or participation in a clinical trial within the last thirty days before the start of this study
• Symptomatic coronary artery disease, cardiac arrhythmias uncontrolled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease)
• Severe non-compensated pulmonary disease (IVC \<55%, DLCO \<40%)
• Third space fluid accumulation \>500 ml
• Hypersensitivity to study treatment or any component of the formulation
• Taking any medications likely to cause interactions with the study medication
• Known or persistent abuse of medication, drugs or alcohol

Sponsors & Collaborators

• University Hospital Freiburg: lead
• German Federal Ministry of Education and Research: collaborator
• International Extranodal Lymphoma Study Group (IELSG): collaborator

Study Sites (2)

University Hospital Freiburg - Department for Hematology, Oncology and Stem cell Transplantion

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Klinikum Stuttgart, Clinic of Hematology, Oncology and Palliative Care, Stuttgart Cancer Center / Tumor Center Eva Mayr-Stihl

Stuttgart, Baden-Wurttemberg, 70174, Germany

RECRUITING

Related Publications (6)

• Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. doi: 10.1200/JCO.2006.06.2117. Epub 2006 Jul 24.

  PMID: 16864853 RESULT

• Illerhaus G, Muller F, Feuerhake F, Schafer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. doi: 10.3324/haematol.11771.

  PMID: 18166803 RESULT

• Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-2675. doi: 10.1093/annonc/mds059. Epub 2012 Apr 3.

  PMID: 22473593 RESULT

• Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. doi: 10.1200/JCO.2007.13.5533. Epub 2008 Apr 14.

  PMID: 18413641 RESULT

• Motomura K, Natsume A, Fujii M, Ito M, Momota H, Wakabayashi T. Long-term survival in patients with newly diagnosed primary central nervous system lymphoma treated with dexamethasone, etoposide, ifosfamide and carboplatin chemotherapy and whole-brain radiation therapy. Leuk Lymphoma. 2011 Nov;52(11):2069-75. doi: 10.3109/10428194.2011.596967. Epub 2011 Jul 12.

  PMID: 21745167 RESULT

• Schorb E, Finke J, Ferreri AJ, Ihorst G, Mikesch K, Kasenda B, Fritsch K, Fricker H, Burger E, Grishina O, Valk E, Zucca E, Illerhaus G. High-dose chemotherapy and autologous stem cell transplant compared with conventional chemotherapy for consolidation in newly diagnosed primary CNS lymphoma--a randomized phase III trial (MATRix). BMC Cancer. 2016 Apr 21;16:282. doi: 10.1186/s12885-016-2311-4.

  PMID: 27098429 DERIVED

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Gerald Illerhaus, PhD

  Representative of Sponsor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elisabeth Schorb, PhD

CONTACT

0049761270; elisabeth.schorb@uniklinik-freiburg.de

Elvira Burger

CONTACT

0049761270; elvira.burger@uniklinik-freiburg.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Trial Coordinator

Study Record Dates

• First Submitted: August 14, 2015
• First Posted: August 25, 2015
• Study Start: July 1, 2014
• Primary Completion: November 1, 2017
• Study Completion: December 1, 2019
• Last Updated: August 25, 2015

Record last verified: 2015-08

Locations

DE (2)