Effectiveness and Safety of MMSCs for Enhancing Hematopoietic Recovery and Prophylaxis of Neutropenic Enterocolitis

Phase 1

• Conditions: Myeloablative Chemotherapy Induced Bone Marrow Aplasia; Neutropenic Enterocolitis
• Interventions: Procedure: Peripheral blood stem cell mobilisation and collection; Drug: High-dose chemotherapy; Drug: Bone marrow derived allogeneic MMSCs infusion; Procedure: Autologous peripheral blood stem cells infusion

• Registration Number: NCT02145923
• Lead Sponsor: Burnasyan Federal Medical Biophysical Center

Brief Summary

Subjects will undergo peripheral blood stem cell mobilisation and collection with subsequent high-dose chemotherapy. After finalization of high-dose chemotherapy subjects will receive bone marrow derived allogeneic multipotent mesenchymal stromal cells intravenous infusion two hours prior to autologous peripheral blood cells infusion. This is a single arm study with no control. All patients receive cell therapy.

Detailed Description

Patients with verified diagnosis Hodgkin's lymphoma or non-Hodgkin's lymphoma will undergo peripheral blood stem cell mobilisation and collection (chemotherapy + G-CSF or G-CSF+Plerixafor).

After that high-dose chemotherapy will be performed according to protocols ICE and BEAM (standard scheme).

Patient will receive bone marrow derived allogeneic multipotent mesenchymal stromal cells infusion 48 hours after last administration of cytotoxic agent . Number of cells calculated according to patient's body weight (1,5-2,0 mln of cells/kg), time of infusion - 30 minutes. Two hours later patient will receive autologous peripheral blood cells infusion.

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-05-21
• Study First Submitted QC: 2014-05-22
• Study First Posted: 2014-05-23
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-09
• Last Update Posted: 2015-06-10
• Primary Completion: 2016-06
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Patient suffers from Hodgkin's lymphoma, non-Hodgkin's lymphoma with complete or partial remission.
• Patient is candidate to high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation.
• Absence of infection, cardiovascular, respiratory, renal and hepatic dysfunctions, focal neurological symptoms.
• Karnofsky score at least 70.
• Patient successfully undergone mobilization of peripheral blood stem cells.
• Patient is familiar with Participant information sheet.
• Patient signed informed consent form.

Non-inclusion Criteria:

• Severe chronic comorbidity with symptoms of organ or system failure.
• Significant abnormalities in laboratory tests.
• Participation in other clinical trials (or intake of study drugs) within prior 3 months.
• Conditions restricting commitment to participating in the trial (dementia, neuropsychiatric disorders, drug and alcohol abuse)
• Patients with malignant solid tumors.
• Patients with medical history of heterotopic ossification.

Exclusion Criteria

• Progression or relapse of lymphoma during therapy.
• Confirmed syphilis, HIV, hepatitis B or C infection
• Absence of clinical and laboratory signs of hematopoietic recovery and persistent enterocolitis at day 14 after the manipulation (Visit 15). While the patient remains in the hospital and continues treatment according to requirements of standard therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
allogeneic MMSCs infusion	High-dose chemotherapy	Subjects will undergo peripheral blood stem cell mobilisation and collection with subsequent high-dose chemotherapy. After finalization of high-dose chemotherapy subjects will receive bone marrow derived allogeneic multipotent mesenchymal stromal cells intravenous infusion two hours prior to autologous peripheral blood cells infusion.
allogeneic MMSCs infusion	Autologous peripheral blood stem cells infusion	Subjects will undergo peripheral blood stem cell mobilisation and collection with subsequent high-dose chemotherapy. After finalization of high-dose chemotherapy subjects will receive bone marrow derived allogeneic multipotent mesenchymal stromal cells intravenous infusion two hours prior to autologous peripheral blood cells infusion.
allogeneic MMSCs infusion	Peripheral blood stem cell mobilisation and collection	Subjects will undergo peripheral blood stem cell mobilisation and collection with subsequent high-dose chemotherapy. After finalization of high-dose chemotherapy subjects will receive bone marrow derived allogeneic multipotent mesenchymal stromal cells intravenous infusion two hours prior to autologous peripheral blood cells infusion.
allogeneic MMSCs infusion	Bone marrow derived allogeneic MMSCs infusion	Subjects will undergo peripheral blood stem cell mobilisation and collection with subsequent high-dose chemotherapy. After finalization of high-dose chemotherapy subjects will receive bone marrow derived allogeneic multipotent mesenchymal stromal cells intravenous infusion two hours prior to autologous peripheral blood cells infusion.

Primary Outcome Measures

Name	Time	Method
Number of serious adverse events (SAEs) and serious adverse reactions (SARs)	2 weeks after treatment

Secondary Outcome Measures

Name	Time	Method
Time of hematopoietic recovery	Follow up to completion (up to 3 months after treatment)	Monitoring of time of hematopoietic recovery assessed by complete blood count
Transfusion needs	Follow up to completion (up to 3 weeks after treatment)	Monitoring of frequency (number of participants) of transfusion needs during neutropenic period
Neutropenic enterocolitis	Follow up to completion (up to 3 months after treatment)	Monitoring of frequency (number of participants) and severity of neutropenic enterocolitis during the study period
Infectious complications	Follow up to completion (up to 3 months after treatment)	Monitoring of frequency and severity of infectious complications during the study period. Frequency of infectious complications will be represented in number of infections verified by clinical, instrumental examination and/or laboratory methods.

Trial Locations

Locations (1)

State Research Center Burnasyan Federal Medical Biophysical Center FMBA of Russia; 🇷🇺 Moscow, Russian Federation