Phase Ib/II Study of the Efficacy and Safety of the R-CMC544/R-GEMOX Combination in Diffuse Lage B-cell Lymphoma at First or Second Relapse - Full Text View

Purpose

The purpose of this study is to determine the recommended dose of CMC544 administered in combination with rituximab (R-CMC544), and in alternance with rituximab, gemcitabine and oxaliplatin (R-GEMOX) in the first phase of the study. After that, efficacy and safety of this combination will be evaluated preliminarily in patients with DLBCL in relapse or refractory, who are no candidates for autologous transplant.

Condition	Intervention	Phase
Diffuse Large B-Cell Lymphoma	Drug: Rituximab, CMC544, Gemcitabine and Oxaliplatine	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multi-center, Phase IB/II, Open Label, Single Arm Study of Inotuzumab Ozogamicin Plus Rituximab (R-CMC544)Alternating With Gemcitabine-oxaliplatin Plus Rituximab(R-GEMOX)in Patients Aged From 18 to 80 Years With CD20 and CD22 Positive Diffuse Large B-cell Lymphoma (DLBCL) in Relapse After/Refractory to 1ST or 2ND Line Treatment, Who Are no Candidates for Autologous Transplant.

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Oxaliplatin Gemcitabine Gemcitabine hydrochloride Rituximab

U.S. FDA Resources

Further study details as provided by The Lymphoma Academic Research Organisation:

Primary Outcome Measures:

Determination of the Recommended Dose of R-CMC544 [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
Determination of recommended dose will be based on safety parameters and particularly on incidence of DLTs

Secondary Outcome Measures:

OVERALL RESPONSE RATE [ Time Frame: Up to 32 weeks ] [ Designated as safety issue: No ]
Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999 and 2007). Patient is defined as a responder if he/she has a complete response (CR) or partial response (PR) at the end of treatment. A descriptive analysis will also be performed considering as non-responders all patients who relapsed or died during treatment phase even if they were prematurely withdrawn as responder
PROGRESSION-FREE SURVIVAL [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
Progression-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.
EVENT FREE SURVIVAL [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
Event-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.
OVERALL SURVIVAL [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
Overall survival will be measured from the date of inclusion to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of the last contact.
COMPLETE RESPONSE RATE [ Time Frame: 30 or 32 weeks (depending on induction cycle length) ] [ Designated as safety issue: No ]
Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 2007)).

Patient without response assessment (due to whatever reason) will be considered as nonresponder.

Estimated Enrollment:	40
Study Start Date:	December 2012
Estimated Study Completion Date:	October 2016
Estimated Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: R-CMC544 and R-GEMOX Treatment with R-CMC544 and R-GEMOX	Drug: Rituximab, CMC544, Gemcitabine and Oxaliplatine 2 cycles of induction of 56 days each, starting with the administration of R-CMC544 on day 1, followed by the administration of R-GEMOX on day 29 and 43. 2 cycles of consolidation of 56 days each, starting with the administration of R-CMC544 on day 1, followed by the administration of R-GEMOX on day 29 and 43.

Detailed Description:

This study is a multicenter, phase Ib/II, open-label, single arm trial evaluating the efficacy and safety of R-CMC544 alternated with R-GEMOX in patients with CD20 and CD22 positive DLBCL in relapse after/refractory to 1st or 2nd line treatment, who are no candidates for autologous transplant.

The study consists of 2 phases. In part 1 (potential dose de-escalation phase) subjects will be enrolled at a fixed dose of CMC544. In case of occurrence of dose limiting toxicity (DLT), cohorts of 3 to 6 subjects will evaluate a de-escalating dose of CMC544 in combination with set doses of rituximab, gemcitabine and oxaliplatin in order to obtain the MTD or recommended dose of CMC544 in this regimen. In part 2 (dose expansion phase) further safety and preliminary efficacy data of the proposed combination will be analyzed.

All patients will receive two 56 day induction cycles of alternating R-CMC544 (given on day 1) and R-GEMOX (given on day 29 and 43). Patients who obtain CR or PR, will then go on a consolidation of another two 56 day cycles of alternating R-CMC544 (given on day 1) and R-GEMOX (given on day 29 and 43).

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically documented CD20 and CD22 positive diffuse large B-cell lymphoma, according to WHO classification. CD20 and CD22 immunophenotyping at initial diagnosis is acceptable. If such prior documentation is not available, then the immunophenotyping at relapse must be established by fine-needle aspirate or biopsy or by circulating CD20 and CD22 positive NHL cells from peripheral blood during screening. Upon registration the pathological report confirming the diagnosis, must be available
In first or second relapse or refractory to first and/or second line treatment. Refractory is defined as having exhibited less than or PR to a prior rituximab containing regimen or having relapsed within 6 months of the last dose of a prior rituximab containing regimen.
Measurable disease by bidimensional transverse CT scan assessment
Not eligible for autologous transplantation.
Previously treated with a chemotherapy regimen containing anthracyclines and rituximab.
Aged 18 - 80 years.
ECOG performance status 0 to 2.
Minimum life expectancy of 3 months.
Signed written informed consent.

Exclusion Criteria:

Burkitt, mantle cell and T-cell lymphomas.
Central nervous system or meningeal involvement by the lymphoma.
Contraindication to any drug contained in the R-GEMOX combination chemotherapy.
Treatment with any investigational drug within 30 days before the first planned cycle of chemotherapy and during the study.
Nitrosurea or mitomycin C administration within 6 weeks prior to study start.
Major debulking surgery within 3 weeks of treatment.
Any of the following lab abnormalities (unless related to the lymphoma or bone marrow infiltration):

Absolute neutrophil count (ANC) < 1.500/µL (1,5.109/L).

Platelet count < 100.000/µL (100.109/L).

Creatinin level > 150 µmol/L (1,7 mg/dL) or 1,5 - 2,0x ULN.

Total bilirubin level > 30 µmol/L (1,8 mg/dL) or 1,5x ULN.

Serum AST/SGOT or ALT/SGPT >2,5x ULN.

Documented infection with HIV, active hepatitis B or C infection.
Any serious active disease or co-morbid medical condition that, according to the investigator's decision, will substantially increase the risk associated with the subject's participation in the study. Prior history of malignancies other than lymphoma with the exception of non-melanoma skin tumors (basal cell or squamous cell carcinoma of the skin) or stage 0 (in situ) cervical carcinoma unless the subject has been disease-free for 5 or more years..
LVEF less than 50% (measured by echocardiography or scintigraphy).
Previous myocardial infarction or pulmonary hypertension within 6 months before the first dose of investigational product.
Congestive heart failure NYHA stage III or IV
Known chronic liver disease (eg. Cirrhosis) or suspected alcohol abuse.
Pregnant or lactating females
Men and women who are biologically capable of having children not willing to use an adequate method of birth control during the study and up to 18 months after the last dose of investigational product.
Adult patient unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01562990

Contacts

Contact: Elise Hutasse, Project manager	+33472669333	elise.hutasse@lysarc.org
Contact: Yvain Robreau, Project manager	+33472669333	yvain.robreau@lysarc.org

Locations

Belgium
AZ Sint Jan	Recruiting
Bruges, Belgium, 8000
Contact: Jan VAN DROOGENBROECK, MD 32 (0) 50 452 622 jan.vandroogenbroeck@azsintjan.be
Principal Investigator: Jan VAN jan.vandroogenbroeck@azsintjan.be, MD
Sub-Investigator: Tom LODEWYCK, MD
Sub-Investigator: Dominik SELLESLAG, MD
Sub-Investigator: Achiel VAN HOOF, MD
University Hospital Gent	Recruiting
Gent, Belgium, 9000
Contact: Fritz OFFNER, MD 0032 93 32 21 32 fritz.offner@ugent.be
Principal Investigator: Fritz OFFNER, PhD
CHU Mont-Godinne	Recruiting
Yvoir, Belgium
Contact: Marc ANDRE 00 32 81 42 38 64 marc.andre@uclouvain.be
Principal Investigator: Marc ANDRE, MD
Sub-Investigator: Christian CHATELAIN, MD
Sub-Investigator: Chantal DOYEN, MD
Sub-Investigator: Carlos GRAUX, MD
Sub-Investigator: Anne SONET, MD
France
Hôpital Henri Mondor	Recruiting
Créteil, France, 94010
Contact: Corinne HAIOUN, PhD 01 49 81 41 54 corinne.haioun@hmn.aphp.fr
Principal Investigator: Corinne HAIOUN, PhD
Sub-Investigator: Karim BELHADJ, MD
Sub-Investigator: Jehan DUPUIS, MD
Sub-Investigator: Isabelle GAILLARD, MD
Sub-Investigator: Violaine SAFAR, MD
CHU de Dijon	Recruiting
Dijon, France, 21000
Contact: Olivier CASASNOVAS, Md 03 80 29 30 31
Principal Investigator: Olivier CASASNOVAS, MD
Sub-Investigator: Jean-Noël BASTIE, MD
Sub-Investigator: Denis CAILLOT, MD
Sub-Investigator: Emmanuelle FERRANT, MD
Sub-Investigator: Ingrid LAFON, MD
Sub-Investigator: Agathe WAULTIER, MD
CHRU de Lille	Recruiting
Lille, France, 59037
Contact: Franck MORSCHHAUSER, MD 03 20 44 57 13 franck.morschhauser@chru-lille.fr
Principal Investigator: Franck MORSCHHAUSER, MD
Sub-Investigator: Louis TERRIOU, MD
Sub-Investigator: Sabine TRICOT, MD
CHU Lyon - Sud	Recruiting
Lyon, France, 69495
Contact: Bertrand COIFFIER, PhD 04 78 86 43 08 bertrand.coiffier@chu-lyon.fr
Principal Investigator: Bertrand COIFFIER, PhD
Sub-Investigator: Fadhéla BOUAFIA, MD
Sub-Investigator: Marie BOUTELOUP, MD
Sub-Investigator: Gilles SALLES, PhD
Sub-Investigator: Sophie DUPIRE, MD
Sub-Investigator: Daniel ESPINOUSE, MD
Sub-Investigator: Lionel KARLIN, MD
Sub-Investigator: Anne-Sophie MICHALLET, MD
Sub-Investigator: Catherine TRAULLE, MD
CHU Hôtel Dieu	Recruiting
Nantes, France, 44093
Contact: Setven LE GOUILL, MD 02 40 08 32 71 steven.legouill@chu-nantes.fr
Principal Investigator: Steven LE GOUILL, MD
Sub-Investigator: Nicolas BLIN, MD
Sub-Investigator: Aline CLAVERT, MD
Sub-Investigator: Viviane DUBRUILLE, MD
Sub-Investigator: Thomas GASTINNE, MD
Sub-Investigator: Béatrice MAHE, MD
Sub-Investigator: Philippe MOREAU, MD
Sub-Investigator: Virginie ROLAND, MD
CHU Pontchaillou	Not yet recruiting
Rennes, France, 35003
Contact: Roche HOUOT, MD 02 99 28 98 73 roch.houot@chu-rennes.fr
Principal Investigator: Roch HOUOT, MD
Sub-Investigator: Marc BERNARD, MD
Sub-Investigator: Xavier CAHU, MD
Sub-Investigator: Charles DAURIAC, MD
Sub-Investigator: Sophie De GUIBERT, MD
Sub-Investigator: Martine ESCOFFRE-BARBE, MD
Sub-Investigator: Stanislas NIMUBONA, MD
Centre Henri Becquerel	Recruiting
Rouen, France, 76038
Contact: Hervé TILLY, PhD 02 32 08 22 02 herve.tilly@chb.unicancer.fr
Principal Investigator: hervé TILLY, PhD
Sub-Investigator: Oana BREHAR, MD
Sub-Investigator: Nathalie CARDINAEL, MD
Sub-Investigator: Nathalie CONTENTIN, MD
Sub-Investigator: Marie-Laure FONTOURA, MD
Sub-Investigator: Carole FRONVILLE, MD
Sub-Investigator: Fabrice JARDIN, MD
Sub-Investigator: Pascal LENAIN, MD
Sub-Investigator: Stéphane LEPRETRE, MD
Sub-Investigator: Emilie LEMASLE, MD
Sub-Investigator: Aspasia STAMATOULLAS, MD
CHU Brabois	Recruiting
Vandoeuvre les nancy, France, 54511
Contact: Serge BOLOGNA, MD
Principal Investigator: Serge BOLOGNA, MD
Sub-Investigator: Caroline BONMATI, MD
Sub-Investigator: Pierre FEUGIER, PhD
Sub-Investigator: Cyrille HULIN, MD
Sub-Investigator: Dana RANTA, MD

Sponsors and Collaborators

The Lymphoma Academic Research Organisation

Pfizer

Investigators

Study Chair:	Fritz OFFNER, MD	Lymphoma Study Association
Study Chair:	Corinne HAIOUN, PhD	Lymphoma Study Association

More Information

Additional Information:

LYSA (Lymphoma Study Association) website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:	NCT01562990 History of Changes
Other Study ID Numbers:	CMC-R-GEMOX, 2011-003849-18
Study First Received:	March 20, 2012
Last Updated:	January 9, 2013
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products France: L’Agence nationale de sécurité du médicament et des produits de santé

Additional relevant MeSH terms:

Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Oxaliplatin
Rituximab
Antimetabolites, Antineoplastic

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 19, 2013