Therapy of Non-Hodgkin-Lymphoma by Combination of Lenalidomide + Rituximab, Dexa, High-dose ARA-C and CisP

NCT02983097 | Terminated Phase 1

• 2 other identifiers: DSHNHL 2008 R62009-010824-25
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 12

Brief Summary

The goal of this study is to evaluate efficacy and safety of the combination of lenalidomide, an immunomodulatory drug (IMiD) with a standard immunochemotherapy treatment, called R-DHAP. R-DHAP consists of a monoclonal antibody called Rituximab and chemotherapy consisting of Dexamethasone, high dose Cytarabine, often called Ara-C, and platinum based chemotherapy, either cisplatinum, or, if treatment with cisplatinum is contraindicated, carboplatinum.

Conditions

Diffuse Large B-cell Lymphoma (DLBCL); Follicular Lymphoma Grade III (FL III°); Mantle Cell Lymphoma (MCL), Blastoid Variant; Burkitt Lymphoma (BL); Aggressive Marginal Zone Lymphoma (MZL)

Keywords

lymphoma; relapse; recurrence; progress; progressive; b-cell lymphoma; chemotherapy; immunotherapy; IMiD; Salvage chemotherapy; peripheral stem cell mobilization; lenalidomide; Rituximab; CD20; Cytarabine; Ara-C; platinum-based chemotherapy; Cisplatin; Carboplatin; Cisplatinum; Carboplatinum; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  The percentage of patients which showed either a partial remission (PR), a complete remission with remaining uncertainty (CRu) or a complete remission (CR) after study treatment.

  78 - 85 days + 2 years Follow Up

• Maximum tolerated dose (MTD)

  The maximum dose of lenalidomide tolerated with acceptable toxicity during phase 1 of this study. The MTD established in phase 1 of this study will be administered to 50 patients in phase 2 of this study.

  78 - 85 days

Secondary Outcomes (10)

• Rate of complete remission

  78 - 85 days + 2 years Follow Up

• Rate of primary progression

  78 - 85 days + 2 years Follow Up

• Rate of treatment related deaths

  78 - 85 days + 2 years Follow Up

• Relapse Rate

  78 - 85 days + 2 years Follow Up

• Overall Survival

  78 - 85 days + 2 years Follow Up

Study Arms (1)

R²-DHAP

EXPERIMENTAL

Combination treatment with immunochemotherapy (R-DHAP) and lenalidomide Dosage: Rituximab 375 mg/m² day 1, i.v. Cisplatin 100 mg/m² or Carboplatin AUC5 day 2, i.v. Cytarabine 2000 mg/m², administered twice, on day 3, i.v. Dexamethasone 40 mg, days 2-5, p.o. Lenalidomide 5-20 mg, day 1-7 / day-6-+7, p.o. PEG-Filgrastim 6 mg, day 6, s.c. peripheral stem cell collection after cycle 1 or 2

Drug: Rituximab; Drug: Cisplatin; Drug: Carboplatin; Drug: Dexamethasone; Drug: Cytarabine; Drug: Lenalidomide; Drug: PegFilgrastim; Procedure: peripheral stem cell collection

Interventions

Rituximab DRUG

Rituximab 375 mg/m²

Also known as: MabThera

R²-DHAP

Cisplatin DRUG

Cisplatinum 100 mg / m²

Also known as: Cisplatinum

R²-DHAP

Carboplatin DRUG

Carboplatinum AUC5

Also known as: Carboplatinum

R²-DHAP

Dexamethasone DRUG

Dexamethasone 40 mg

R²-DHAP

Cytarabine DRUG

Cytarabine 2000 mg/m², administered twice

Also known as: Cytarabin, Ara-C

R²-DHAP

Lenalidomide DRUG

5-20 mg administered either d1-d7, or d-6-d7

Also known as: Revlimid

R²-DHAP

PegFilgrastim DRUG

PegFilgrastim 6 mg

Also known as: Neulasta

R²-DHAP

peripheral stem cell collection PROCEDURE

collection of peripheral stem cells for autologous stem cell transplantation

Also known as: peripheral stem cell apheresis, hematopoetic stem cell apheresis, peripheral hematopoetic stem cell apheresis

R²-DHAP

Eligibility Criteria

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

You may qualify if:

• Age: 18-70
• Risk groups: All risk groups
• histology: diagnosis or a recurrent or primary progressive aggressive b-cell non-hodgkin lymphoma, in particular
• follicular lymphoma grade III
• diffuse large b-cell lymphoma
• burkitt lymphoma
• mantle cell lymphoma, blastoid variant
• aggressive marginal zone lymphoma
• Performance status: ECOG 0-2
• Criteria for women of childbearing potential:
• Women of childbearing potential have to:
• understand the teratogenic risk associated with the study therapy, especially lenalidomide
• understand the need of reliable, uninterrupted birth control from 4 weeks prior to the start of the study drug, during the duration of the study treatment, and 4 weeks after completion of study treatment, and be able to reliably use birth control, except if the patient commits to absolute sexual abstinence, confirmed on a monthly basis
• The following are effective methods of contraception:
• implant

You may not qualify if:

• pregnant or lactating females
• already initiated salvage lymphoma therapy (except prephase as specified in this study)
• serious accompanying disorder or impaired organ function causing significant clinical problems and reduced lyfe expectancy, in particular: heart: angina pectoris CCS\>2 cardiac failure NYHA\>2 and/or EF\<45% lungs: FeV1\<60%, diffusion capacity \<50% of the reference values kidneys: creatinine\>2 times the upper reference limit liver: bilirubin \>2 times the upper reference limit
• platelets \<80000/mm³, leukocytes \<2500/³
• CNS involvement of lymphoma
• known hypersensitivity to the medications to be used
• known HIV-positivity
• suspicion that patient compliance will be poor, especially that rules for effective contraception will not be followed
• simultaneous participation in other treatment studies
• non-conformity to eligibility criteria

Sponsors & Collaborators

• Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH: lead
• Celgene: collaborator
• Amgen: collaborator

Study Sites (12)

Diakonie Krankenhaus Bremen

Bremen, 28239, Germany

Location

Klinikum Chemnitz

Chemnitz, 09113, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Klinikum Frankfurt/Oder

Frankfurt (Oder), 15236, Germany

Location

Universitätsklinikum Göttingen

Göttingen, 37075, Germany

Location

Asklepios Klinik St. Georg

Hamburg, 20099, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Westpfalz Klinikum

Kaiserslautern, 67665, Germany

Location

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

LMU Klinikum München-Großhadern

München, 81377, Germany

Location

Related Links

• Homepage of the "Kompetenznetz Maligne Lymphome"

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Burkitt Lymphoma; Lymphoma; Recurrence; Lymphoma, B-Cell

Interventions

Rituximab; Cisplatin; Carboplatin; Dexamethasone; Cytarabine; Lenalidomide; pegfilgrastim

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Bertram Glaß, MD

  AK St.Georg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2013
• First Posted: December 6, 2016
• Study Start: November 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: April 28, 2015
• Last Updated: January 19, 2018

Record last verified: 2016-12

Locations

DE (12)