Trial Information

A Randomized Double Blind Placebo Controlled Phase III Study of Efficacy of Lactobacillus CD2 Lozenges in Preventing High-Dose Chemotherapy Induced Oral Mucositis in Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplantation

Study Design Placebo controlled double blind randomized, multi center clinical trial.

Study Population and Number of Subjects Total of 108 patients undergoing myeloablative
allogeneic or autologous hematopoietic stem cell transplantation and receiving high-dose
chemotherapy as conditioning regimen at AIIMS (departments of Medical Oncology and
Hematology) will be enrolled for the study and will be equally divided in two groups (drug
and placebo).

Study Center The study will be carried at Departments of Medical Oncology and Hematology of
All India Institute of Medical Sciences, New Delhi, India.

More centers are likely to be added.

Study Objectives To test whether the probiotic Lactobacillus CD2 (drug) lozenges can reduce
the incidence and severity of conditioning therapy induced oral mucositis in patients
undergoing haematopoietic stem cell transplantation.

Investigational Product Drug: The trial medication is in the form of lozenge, which is
supposed to be dissolved by itself in mouth.

It contains not less than 2x109 (2 billion) viable cells of Lactobacillus CD2 as active
ingredient.

Placebo: The placebo is a mix of sugars and salts used as excipients in the active
formulation.

Note: Placebo and drug lozenges will be similar in physical appearance and color.

Dose of Study drug The daily dose of trial medications will be 4-6 lozenges per day, one
lozenge to be taken every 2-3 hours preferably not before the meal. The lozenge should be
kept in mouth for it to dissolve by itself. A hot beverage (e.g. tea, coffee, milk etc.)
should not be taken for at least half an hour before and after the medication since elevated
temperature can inactivate the bacteria.

Duration of treatment The treatment will start 7 days before starting chemotherapy for
conditioning regime of HSCT and will continue till resolution of mucositis or Day+24 post
stem cell infusion which-ever is earlier.

Efficacy Assessments

Clinical activity will be defined as reduction in the incidence and severity of chemotherapy
induced mucositis in HSCT patients. Most recent version of CTCAE; clinical score of CTC
V4.03 ( as also outlined in CTCAE version 3.0) will be used for mucositis assessment.
Also,WHO and Oral Mucositis assessment score will be recorded. The study will have the
following primary and secondary endpoints:

Primary endpoint

1. Determine the incidence of grade III and IV mucositis in patients undergoing allogeneic
or autologous haematopoietic stem cell transplantation in two groups.

Secondary endpoint

1. Determine the incidence of Grade I and II mucositis in patients undergoing allogenic or
autologous haematopoietic stem cell transplantation in two groups.

2. Duration of and time period for healing of chemotherapy induced oral mucositis.

3. Determine incidence and severity of dysphagia and requirement of IV antibiotics in two
groups

Safety Assessments

1. Medical History

2. Physical Examination

3. Vital Signs (blood pressure, pulse rate and respiratory rate)

4. Laboratory Examinations

5. Adverse Events