Clinical trial NCT02752243: CIK-Cells in Relapsing Patients With Acute Leukemia or Myelodysplastic Syndromes After SCT.
Official title: A Prospective Phase I/II Study to Investigate the Feasibility, Safety and Efficacy of IL-15 Activated Cytokine Induced Killer (CIK) Cells in Relapsing Patients With Acute Leukemia or Myelodysplastic Syndromes After Allogeneic SCT
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndromes
Acute Leukemia
Keywords: acute leukemia
myelodysplastic syndrome (MDS)
Stem Cell Transplantation
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2016-04-26
Enrollment: 32
Sex: ALL
Minimum age (years): 0
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Multi-site, non-randomized Phase I/II study involving children and adults.

Detailed description: This is a phase I/II multicenter-study to investigate the feasibility safety and efficacy of interleukin (IL)-15 activated CIK cells in patients with acute leukemia or myelodysplastic syndrome (MDS) showing evidence of relapse after allogeneic stem cell transplantation (SCT).

CIK cell infusions will be given with an interval of 4-6 weeks according to a dose escalation schedule in patients with impending relapse after allogeneic SCT. In presence of acute graft versus host disease (aGvHD) ≥ grade II, the next scheduled infusion will not be administered.

Eligibility criteria: Inclusion Criteria:

Acute leukemia and MDS patients with molecular or cytogenetic relapse in peripheral blood (PB) or bone marrow (BM) samples obtained during monitoring for relapse after allogeneic SCT.

MRD detected by Ig/TCR gene rearrangement testing or any detected disease specific DNA or RNA sequence or disease specific cell surface Proteins or mixed recipient chimerism (MC) ≥ 1% and \< 40%, or levels ≥ 10-4 of BCR-ABL/ABL ratio or any other disease specific cytogenetic abnormality will trigger CIK cell interventions.

* Respecting MC, MC = 1% of autologous/recipient signals in PB samples must be confirmed by another PB or BM sample within one week. Patients with MC = 1% of autologous/recipient signals in CD33+ and/or CD34+ subpopulations in PB samples must be confirmed by BM analyses within one week. Acute leukemia and MDS patients with MC = 1% of autologous/recipient signals including signals in CD33+ and/or CD34+ subpopulations in BM samples must not be confirmed.
* Acute leukemia and MDS patients with frank relapse ≥ 120 days after allogeneic SCT who achieved complete remission (CR) or blast clearance (i.e. \<5% blasts) in the bone marrow after re-induction chemotherapy.
* All patients must be in complete remission or have achieved blast clearance (i.e. \<5% blasts) in the bone marrow before 1st CIK cell treatment (bone marrow assessment at a maximum of 7 days in advance of 1st treatment is obligatory).
* Patients without immunosuppressive agents and steroids for at least 7 days.
* Patients without chemo- or immune therapy during CIK cell treatment, except patients with thyrosine-kinase inhibitors (TKI) for treatment of BCR-ABL positive leukemia. Last DLI treatment must be 4 weeks before 1st CIK cell treatment.
* Patients with \< grade II aGvHD.
* Patients with Karnowsky or Lansky performance status ≥ 50%.
* Patients and/or his/her legal representative having reviewed the patient information/informed consent form and have had their questions answered and have given written informed consent.

Exclusion Criteria:

* Acute leukemia and MDS patients with hematologic relapse \< day 120 after allogeneic stem cell transplantation.
* Patients with 5% and more malignant cells in a representative bone marrow analysis performed at a maximum of 7 days before 1st CIK cell treatment (obligatory).
* Patients with immunosuppressive agents or steroids.
* Patients with chemo- or immune therapy, except patients with thyrosine-kinase inhibitors (TKI) for BCR-ABL positive leukemias.
* Patients with ≥ grade II GvHD.
* Patients with rapid T cell regeneration and any signs of GvHD
* Patients with Karnowsky or Lansky performance status \< 50%.
* Patients and/or his/her legal representative having reviewed the patient information/informed consent form and have had their questions answered and have not given written informed consent.
* HIV-positive patients.
* HBV/HCV positive patients.
* Patients with prior solid organ transplantation.
* Patients treated with any other investigational product within the last 28 days or five half-lives (whichever is longer).
* Hypersensitivity to any component of the study drug
* Female patients of child-bearing potential not agreeing to use a highly effective method of birth control resulting in a low failure rate (i.e. \< 1%) when used consistently and correctly.
* Male patients with female partners of childbearing potential not agreeing to use a highly effective method birth control resulting in a low failure rate (i.e. \< 1%) when used consistently and correctly.
* Pregnancy/Breastfeeding.
* Patients with severe infections or signs/symptoms of infection within 2 weeks prior to study start.

Primary outcomes:
measure: The occurrence of grade three or four acute Graft versus Host Disease (aGvHD)
timeFrame: two until four weeks after CIK-Cell Infusion
measure: Extensive chronic Graft versus Host Disease (cGvHD)
timeFrame: two until four weeks after CIK-Cell Infusion
Secondary outcomes:
measure: Efficacy of CIK-Cells analyzed by progression free survival
timeFrame: one year
measure: Overall survival
timeFrame: one year
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Ruprecht Karls University, Hospital for children and adolescents, Pediatrics III, Department of Oncology, Haematology, Immunology and Pneumology
state: Baden-Württemberg
city: Frankfurt / Main
country: Germany
facility: Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital Frankfurt
state: Hessen
city: Frankfurt / Main
country: Germany
facility: Internal Medicine II, Department of Hematology, Oncology, Rheumatology and Infectious Diseases, Goethe-University Frankfurt/Main
state: Hessen
city: Duesseldorf
country: Germany
facility: University Medicine Duesseldorf, Department of Paediatric Oncology, Haematology and Immunology, Bone Marrow Transplantation Unit
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: Internal Medicine III, Department of Hematology and Oncology, Johannes Gutenberg University
state: Rhineland Palatinate
Study officials:
References: