acute myeloid leukemia and myelodysplastic syndrome MedDRA version: 16.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864 MedDRA version: 16.0 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 100000004864
Conditions
Interventions
Product Name: Activated NK Cells
Pharmaceutical Form: Infusion
INN or Proposed INN: activated NK-cells
Trade Name: Sendoxan
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Pr
Sponsors
Karolinska University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria to be enrolled in the study: • Must be 18 and = 75 years at the time of signing the informed consent form • Written informed consent • AML or MDS IPSS High (see section 2.1) 1. Refractory to induction therapy 2. Relapse after induction chemotherapy leading to CR and not considered eligible for reinduction 3. Relapse after allogeneic SCT and not considered suitable for reinduction chemotherapy or other conventional relapse therapy. Patients with previous documented graft-versus-host disease (GVHD) are not excluded from this trial, but must not have used systemic immunosuppression (e.g., systemic steroids, calcineurin inhibitors, MTOR-inhibitors, budesonide) for at least 2 weeks, not used anti-thymocyte globulin during the last 3 months. • Fertile patients must use effective contraception prior to, during, and for up to 3 months after completion of study treatment • Related HLA-haploidentical NK cell donor available and willing to undergo lymphaferesis • Karnofsky performance status 70-100% Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: Potential subjects who meet any of the following criteria will be excluded from participating in the study: • Pregnant or lactating females. A negative pregnancy test required. • Expected survival less than two months. • Acute promyelocytic leukemia (APL) • Central nervous system leukemia; Patients with extramedullary relapse are eligible except for those with CNS involvement •Serum/plasma biochemical values as follows 1. Serum creatinine >2.0 mg/dL (177 micromol/L) 2. Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN) 3. Serum total bilirubin >1.5 mg/dL (26 micromol/L), (3.0 mg/dL for patients with Gilbert's syndrome) • HIV, Hepatitis B or Hepatitis C • Uncontrolled systemic infection • Oxygen-dependent • Pleural effusions • Patients with active acute GVHD grade II-IV or moderate to severe chronic GVHD. Patients with grade I acute GVHD or limited chronic GVHD and receiving and receiving locolosed GVHD therapy are not excluded. Patients with heart failure NYHA class III-IV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and in vivo expansion of allogeneic NK cells following titrated intermediate intensity conditioning regims.;Secondary Objective: To determine the anti-leukemic efficacy of allogeneic HLA-haploidentical NK cell infusion following a conditioning regimen with Cy/Flu in patients with high-risk MDS (IPSS high) and AML. To monitor the functional and phenotypic reconstitution of NK cells following infusion. ;Primary end point(s): i) Safety. Non-hematological and hematological toxicity including GVHD will be assessed. ii) In vivo NK cell expansion. NK cell survival and expansion in vivo as monitored by NK cell chimerism in peripheral blood and bone marrow after NK cell infusion.;Timepoint(s) of evaluation of this end point: ii) Day 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Achievement of morphological complete remission at 12 weeks following NK cell infusion. In applicable cases, determine minor and complete cytogenetic response 12 weeks after NK cell infusion. Immunological evaluation of the NK cell repertoire following NK cell infusion as described in section 8.2.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Countries
Sweden
Contacts
Public ContactAndreas Björklund
Center for Hematology, Karolinska University Hospital
Outcome results
None listed