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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)


Phase 2
18 Years
N/A
Not Enrolling
Both
MALT Lymphoma

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Trial Information

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)


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete remission rate

Outcome Time Frame:

week 25

Safety Issue:

No

Principal Investigator

Emanuele Zucca, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

IOSI Oncology Institute of Southern Switzerland

Authority:

Switzerland: Ethikkommission

Study ID:

IELSG38

NCT ID:

NCT01808599

Start Date:

March 2013

Completion Date:

December 2025

Related Keywords:

  • MALT Lymphoma
  • Lymphoma
  • Lymphoma, B-Cell, Marginal Zone

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