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Phase II Study of Chlorambucil and Subcutaneous Rituximab in Patients With Extranodal MALT Lymphoma

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ClinicalTrials.gov Identifier: NCT01808599
Recruitment Status : Active, not recruiting
First Posted : March 11, 2013
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
International Extranodal Lymphoma Study Group (IELSG)

Brief Summary:
Single arm phase II study of Chlorambucil in combination with subcutaneous Rituximab followed by maintenance therapy with subcutaneous Rituximab in patients with histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site, either de novo, or relapsed following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma).

Condition or disease Intervention/treatment Phase
MALT Lymphoma Drug: Chlorambucil Drug: Rituximab i.v. Drug: Rituximab s.c. Phase 2

Detailed Description:
The study consists in three parts. In Part A (induction phase I) patients will be treated with Chlorambucil 6 mg/m2 daily p.o for 42 consecutive days (weeks 1-6) in combination with intravenous Rituximab 375mg/m2 on day 1 week 1 followed by subcutaneous Rituximab 1400mg on days 8, 15 and 22 (day 1 of weeks 2, 3 and 4). After restaging (CT scan to be performed during weeks 7-8, i.e. between d42 and d55), responding patients (CR, CRu, PR) and those with stable disease will be treated in part B (induction phase II). In part B, starting from d56, (month 3) patients will receive Chlorambucil 6 mg/m2 daily p.o for 14 consecutive days (d1-14) every 28 days for 4 cycles in combination with subcutaneous Rituximab 1400mg on day 1 of each 28-day cycle. After restaging (CT scan to be performed at the end of month 6) responding patients and those with stable disease will be treated in part C. In Part C (maintenance phase) patients will be treated with subcutaneous Rituximab 1400mg every two months for 2 years (in total 12 injections). During maintenance phase, CT scans will be performed every 12 months and patients responding or with stable disease will stay on treatment for a total of two years as above reported.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Chlorambucil in Combination With Subcutaneous Rituximab Followed by Maintenance Therapy With Subcutaneous Rituximab in Patients With Extranodal Marginal Zone B-cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT Lymphoma)
Study Start Date : December 2013
Actual Primary Completion Date : March 2016
Estimated Study Completion Date : September 2028


Arm Intervention/treatment
Experimental: Chlorambucil, Rituximab i.v., Rituximab s.c.

Chlorambucil 6 mg/m2 daily p.o for 42 consecutive days (weeks 1-6) in combination with intravenous Rituximab 375mg/m2 on days 1, 8, 15 and 22 (day 1 of weeks 1, 2, 3 and 4).

Starting from d56, (month 3) patients will receive Chlorambucil 6 mg/m2 daily p.o for 14 consecutive days (d1-14) every 28 days for 4 cycles in combination with subcutaneous Rituximab 1400mg on day 1 of each 28-day cycle. Therefore subcutaneous Rituximab 1400mg every two months for 2 years (in total 12 injections).

Drug: Chlorambucil
Drug: Rituximab i.v.
Drug: Rituximab s.c.



Primary Outcome Measures :
  1. Complete remission rate [ Time Frame: week 25 ]

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: week 25 ]
    Response rate (Complete and partial remission rates) for all patients

  2. Event-free-survival (EFS) [ Time Frame: at 5 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type either de novo, or relapsed following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma) arisen at any extranodal site 1.1 The following patients with gastric MALT Lymphoma can be entered:

    • H. pylori-negative cases, either de novo (non pre-treated) or at relapse following local therapy (i.e., surgery, radiotherapy or antibiotics).
    • H. pylori-positive cases at diagnosis, who failed antibiotic therapy, including

      • Patients with clinical (endoscopic) and histological evidence of disease progression at any time post H. pylori eradication
      • Stable disease with persistent lymphoma at ≥ 1 year post H. pylori eradication
      • Relapse (without H. pylori re-infection), after a remission
      • Patients who failed either first line antibiotics or further local treatment (surgery or radiotherapy) 1.2 Similar consideration may be applied to patients with ocular adnexal lymphoma treated with antibiotics.
  2. Measurable or evaluable disease. Measurable disease in at least two perpendicular dimensions on an imaging scan is defined as: lymph node or nodal mass bi-dimensional measurement with > 1.5 cm in longest transverse diameter or the short diameter must measure > 10 mm regardless of the longest transverse diameter.
  3. Any stage (Ann Arbor I-IV) (see Appendix A)
  4. Age ≥ 18
  5. Life expectancy of at least 1 year
  6. ECOG performance status 0-2 (see Appendix B)
  7. Adequate bone marrow function (WBC >3.0x109/L, ANC >1.5x109/L, PLT >100x109/L), unless due to lymphoma involvement
  8. Adequate kidney (serum creatinine <1,5x upper normal) and liver function (ASAT/ALAT <2,5 upper normal, total bilirubin <2,5x upper normal), unless due to lymphoma involvement
  9. For women of childbearing potential only: negative serum pregnancy test done within 7 days prior to study drugs administration or within 14 days if with a confirmatory urine pregnancy test within 7 days prior to the first study drugs administration
  10. Fertile male or female patients of childbearing potential and their partners must use two forms of contraception during the study and for at least 12 months after the last dose of subcutaneous rituximab.

    For appropriate methods of contraception considered acceptable, see Appendix C. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 12 months after study participation, the patient should inform the treating physician immediately.

    Female patients of childbearing potential are defined as follows:

    • Pre-menopausal women (patients with regular menstruation, patients after menarche with amenorrhea or irregular cycles, patients using a contraceptive method that precludes withdrawal bleeding
    • Women who have had tubal ligation

    Female patients may be considered to NOT be of childbearing potential for the following reasons:

    • The patient has undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy
    • The patient is medically confirmed to be menopausal (no menstrual period) for 24 consecutive months
  11. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  1. Evidence of histologic transformation to a high grade lymphoma
  2. Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer
  3. Prior chemotherapy
  4. Prior immunotherapy with any anti-CD20 monoclonal antibody
  5. Prior radiotherapy in the last 6 weeks
  6. Use of corticosteroids during the last 28 days, unless prednisone chronically administered at a dose <20 mg/day for indications other than lymphoma or lymphoma-related symptoms
  7. Evidence of clinically significant cardiac disease, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry
  8. Evidence of symptomatic central nervous system (CNS) disease
  9. Evidence of active opportunistic infections
  10. Known HIV infection
  11. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded
  12. Positive serology for hepatitis C (HC) defined as a positive test for HCAb, confirmed by HC RIBA immunoblot assay on the same sample.
  13. Pregnant or lactating status
  14. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  15. Fertile men or women of childbearing potential who do not agree to use a highly effective measure of contraception (such as oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) throughout the study and for at least 12 months after the last dose of subcutaneous rituximab

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01808599


Locations
France
Créteil Hopital Henri Mondor
Créteil, France
Dijon CHU Hopital le Bocage
Dijon, France
Clermont Ferrand CHU Estaing
Estaing, France
Grenoble CHU Pontchaillou
Grenoble, France
Lille CHRU Hopital Claude Dieu
Lille, France
Lyon Centre Léon Bérard
Lyon, France
Pierre Bénite CHU Lyon Sud
Lyon, France
Marseille Paoli Calmettes
Marseille, France
Montpellier CHU Saint Eloi
Montpellier, France
Vandoeuvre lès Nancy CHU Brabois
Nancy, France
Nantes CHU Hotel Dieu
Nantes, France
Paris Hopital Saint Louis
Paris, France
Rennes CHU Pontchaillou
Rennes, France
Rouen Centre Henri Becquerel
Rouen, France
Tours CHU Bretonneau
Tours, France
Italy
AO SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy
Ancona
Ancona, Italy
Centro di Riferimento Oncologico di Aviano
Aviano, Italy
Biella Ospedale degli Infermi
Biella, Italy
Ematologia e CTMO Ospedale Bolzano
Bolzano, Italy
Ematologia Ospedale Businco (Cagliari)
Cagliari, Italy
ARNAS Garibaldi Catania
Catania, Italy
Genova Ematologia I H San Martino
Genova, Italy
Azienda Sanitaria AUSL6 Livorno
Livorno, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola
Meldola, Italy
Istituto Nazionale dei Tumori, Milano
Milano, Italy
Milano Ospedale Policlinico
Milano, Italy
Nocera
Nocera Umbra, Italy
IOV Padova
Padova, Italy
Azienda Ospedaliero-Universitaria di Parma
Parma, Italy
UO Ematologia Ravenna
Ravenna, Italy
Arcispedale Santa Maria Nuova, Azienda Ospedaliera di Reggio Emilia
Reggio Emilia, Italy
Ospedale Infermi Ematologia Rimini
Rimini, Italy
IRCCS/CROB Rionero in Vulture
Rionero in Vulture, Italy
Istituto Regina Elena, Roma, IFO
Roma, Italy
SC Oncoematologia Terni
Terni, Italy
SC Ematologia Torino-Molinette
Torino, Italy
Torino Università, Ematologia 1, AO Città della Salute e della Scienza
Torino, Italy
Switzerland
IOSI - Oncology Institute of Southern Switzerland
Bellinzona, Switzerland, 6500
Sponsors and Collaborators
International Extranodal Lymphoma Study Group (IELSG)
Investigators
Principal Investigator: Emanuele Zucca, MD IOSI Oncology Institute of Southern Switzerland

Responsible Party: International Extranodal Lymphoma Study Group (IELSG)
ClinicalTrials.gov Identifier: NCT01808599     History of Changes
Other Study ID Numbers: IELSG38
First Posted: March 11, 2013    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Non-Hodgkin
Stomach Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Rituximab
Chlorambucil
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action