A phase I/ II study. Efficacy and safety of alpha / betaT- /CD19B-cell depleted allogeneic haematopoietic stem cells transplantation in high risk or relapsed acute leukaemia / MDS followed by an innate donor lymphocyte infusion (iDLI).

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR2463
• Date of registration: 07/08/2010
• Primary sponsor: University Medical Center Utrecht (UMCU)
• Public title: A phase I/ II study. Efficacy and safety of alpha / betaT- /CD19B-cell depleted allogeneic haematopoietic stem cells transplantation in high risk or relapsed acute leukaemia / MDS followed by an innate donor lymphocyte infusion (iDLI).
• Scientific title: A phase I/ II study. Efficacy and safety of alpha / betaT- /CD19B-cell depleted allogeneic haematopoietic stem cells transplantation in high risk or relapsed acute leukaemia / MDS followed by an innate donor lymphocyte infusion (iDLI). - iDLI
• Date of first enrolment: 1/1/2011
• Target sample size: 30
• Recruitment status: complete
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2463
• Study type: intervention
• Study design: Randomised: No; Masking: None; Control: Not applicable; Group: Parallel; Type: Single arm

Countries of recruitment

The Netherlands

Contacts

• Name: L.C.J. Boome, te

• Name: J.H.E. Kuball

Key inclusion & exclusion criteria

Inclusion criteria: 1. Age 18-65 years;

2. Meeting the criteria for a allo-SCT and high risk disease * (see below);

3. WHO performance status ≤ 2;

4. Written informed consent.



*High risk disease as defined by:

1. AML with monosomal karyotype, abnormal 3q26, t(9;22) EVI-1-expression, or complex karyotype in first CR;

2. No CR after first induction cycle chemotherapy;

3. Relapsed AML (in case of second allo-SCT if relapse occurs 6 months after allo-SCT) in second or subsequent CR;

4. MDS with complex karyotype or -7, transfusion dependent or neutropenic with < 10% blasts or in CR after induction therapy;

5. ALL with t(9;22), t(4;11), and other 11q23 abnormalities, and hypodiploidy; complex abnormalities (≥ 5), excluding hyperdiploidy; high WBC at diagnosis (B-ALL > 30x109/l, T-ALL > 100x109/l) in first CR, or no CR after first induction but in CR after rescue chemotherapy;

6. Relapsed ALL (in case of second allo-SCT if relapse occurs 6 months after allo-SCT) in second or subsequent CR.
Exclusion criteria: 1. Relapse of allo-SCT within 6 months after allo-SCT;

2. Relapse acute promyelocyten leukemia;

3. Bilirubin and/or transaminases > 2.5 x normal value;

4. Creatinine clearance < 40 ml/min;

5. Cardiac dysfunction as defined by:

A. Unstable angina;

B. Unstable cardiac arrhythmias.

6. Active, uncontrolled infection;

7. HIV positivity.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Myelodysplastic syndrome (MDS), High risk acute leukemia

Intervention(s)

Selection of T cells and depletion of B-cell in the alloSCT. After that zolendronic acid administations and iDLI after immunosupressive medication is stopped.
Normally there is no selection of T oor B-cells or IDLI.

Primary Outcome(s)

Feasibility and safety of alpha/ betaT-/CD19 B-cell depleted allo-SCT in high risk or relapsed acute leukaemia / MDS followed by an innate donor lymphocyte infusion (iDLI)
by assessing:

1. Time to neutrophil engraftment;

2. Time to platelet engraftment;

3. Time to donor engraftment (chimerism >95%);

4. Time to red blood cell transfusion independence;

5. Incidence and grade of acute GvHD;

6. Incidence and grade of chronic GvHD;

7. Ability to generate and apply an iDLI;

8. Incidence of infections;

9. Transplant related mortality (TRM).

Secondary Outcome(s)

1. Immune reconstitution by counting total number of CD3+ T cells, CD4+ and CD8+ subtyping of T cells, CD3-CD16/56+ (NK cells), alpha / beta T-cells at 3, 6, 12 and 24 months after transplantation;

2. Progression free survival (PFS, i.e. time from transplantation until progression/relapse or death from any cause, whichever comes first);

3. Overall survival (OS) calculated from transplantation. Patients still alive or lost to follow up are censored at the date they were last known to be alive.

Secondary ID(s)

10-257 / NL33076.000.10 ;

Source(s) of Monetary Support

University Medical Center Utrecht (UMCU)