Clinical trial NCT00504803: Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-versus-host Disease
Official title: Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematological Malignancies
Keywords: HCT, nonmyeloablative, mesenchymal stem cells, GVHD
Lead sponsor: University of Liege
Sponsor class: OTHER
First posted: 2007-07-20
Enrollment: 30
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning from HLA-mismatched PBSC or cord blood: a Pilot Study


Eligibility criteria: V.1. Patients

V.1.1. Diseases

Hematological malignancies confirmed histologically and not rapidly progressing:

* AML in CR;
* ALL in CR;
* CML unresponsive/intolerant to Imatinib but not in blast crisis;
* Other myeloproliferative disorders not in blast crisis and not with extensive myelofibrosis;
* MDS with \< 5% blasts;
* Multiple myeloma;
* CLL;
* Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
* Hodgkin's disease.

V.1.2. Clinical situations

* Theoretical indication for a standard allo-transplant, but not feasible because:

  * Age \> 55 yrs;
  * Unacceptable end organ performance;
  * Patient's refusal.
* Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.

V.1.3. Other inclusion criteria

* Male or female; fertile female patients must use a reliable contraception method;
* Age \< 75 yrs.
* Informed consent given by patient or his/her guardian if of minor age.

V.1.4. Exclusion criteria

* Any condition not fulfilling inclusion criteria;
* HIV positive;
* Terminal organ failure, except for renal failure (dialysis acceptable);
* Uncontrolled infection, arrhythmia or hypertension;
* Previous radiation therapy precluding the use of 2 Gy TBI;
* HLA-identical donor.

V.2. PBSC donors

V.2.1. Inclusion criteria

* Related to the recipient (sibling, parent or child) or unrelated;
* Male or female;
* Weight \> 15 Kg (because of leukapheresis);
* Fulfills generally accepted criteria for allogeneic PBSC donation;
* Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.

V.2.2. Exclusion criteria

* Any condition not fulfilling inclusion criteria;
* HIV positive;
* Unable to undergo leukapheresis because of poor vein access or other reasons.

V.2.3. HLA matching

Related or unrelated donors who have 1-2 HLA mismatches, as either :

* One antigenic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1
* One allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1
* Two allelic mismatches at HLA-A or -B or -C or -DRB1 or -DQB1
* One antigenic mismatch + 1 allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1.
* One antigenic mismatch at -DQB1 and one other antigenic mismatch at HLA-A or -B or -C or -DRB1

V.3. Cord blood unit

Banked cord blood units will be used if they fulfill the following criteria:

* No more than 2/6 HLA mismatches (antigenic mismatch at HLA-A or HLA-B or allelic mismatch at HLA-DRB1)
* \> 2.5 x 107 TNC/kg
* Standard validation by FACT/Netcord criteria.

Primary outcomes:
measure: Day-100 incidence of non-relapse mortality
timeFrame: 100 days
Secondary outcomes:
measure: 1. Hematopoietic engraftment and graft rejection. 2. Incidence of grade II-IV and III-IV acute GVHD. 3. Immunologic reconstitution
timeFrame: 365 days
Other outcomes:
Locations:
city: Liege
country: Belgium
facility: CHU Sart Tilman
Study officials:
affiliation: CHU-ULg
name: Frederic Baron, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU-ULg
name: Yves Beguin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU-ULg
name: Chantal Lechanteur, PhD
role: STUDY_CHAIR
affiliation: CHU-ULg
name: Etienne Baudoux, MD
role: STUDY_CHAIR
affiliation: CHU-ULg
name: Evelyne Willems, MD
role: STUDY_CHAIR
References:
citation: Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, Vanbellinghen JF, Hafraoui K, Lejeune M, Gothot A, Fillet G, Beguin Y. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2010 Jun;16(6):838-47. doi: 10.1016/j.bbmt.2010.01.011. Epub 2010 Jan 28.