Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders

Phase 2

Completed

Conditions: Anemia
Myeloproliferative Disorders
Bone Marrow Transplant Failure
Myelodysplastic Syndromes (MDS)
Leukemia, Myeloid
Neural Tube Defects

Interventions: Drug: CIK cells
Drug: Cyclosporine
Drug: Mycophenolate Mofetil
Drug: Thymoglobulin
Radiation: Total Lymphoid Irradiation (TLI)

Registration Number: NCT01392989

Lead Sponsor: Everett Meyer

Brief Summary: Allogeneic stem cell transplantation (transplant of blood cells from another individual) is a treatment option for patients with myelodysplasia or myeloproliferative Disorders. During the course of this study, it will be evaluated whether a particular type of blood cell, called a cytokine-induced killer (CIK) cell, may add benefit to allogeneic stem cell transplantation. CIK cells are present in small quantities in the bloodstream but their numbers can be expanded after a brief period of nurturing in a laboratory.

Detailed Description: Primary Objectives:

To determine the rate of conversion to FDC following infusion of allogeneic CIK cells among patients with MDS, therapy-related myeloid neoplasms, or MPD who receive non myeloablative preparative regimen of TLI / ATG followed by allogeneic HCT and consolidation with allogeneic CIK cells.

Secondary Objectives:

* To determine the 2 year overall survival (OS) and event free survival (EFS)

* To determine the incidence of acute GVHD following infusion of allogeneic CIK cells

* To assess the pre-transplant expression of NKG2D ligands in patients' bone marrow aspirates.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Allogeneic Cytokine-induced Killer Cells (CIK)	Cyclosporine	Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.
Allogeneic Cytokine-induced Killer Cells (CIK)	Total Lymphoid Irradiation (TLI)	Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.
Allogeneic Cytokine-induced Killer Cells (CIK)	Mycophenolate Mofetil	Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.
Allogeneic Cytokine-induced Killer Cells (CIK)	Thymoglobulin	Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.
Allogeneic Cytokine-induced Killer Cells (CIK)	CIK cells	Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.

Primary Outcome Measures

Name	Time	Method
Full Donor Chimerism (FDC)	90 days	Proportion of patients achieving full donor T-cell chimerism (FDC) by on or before Day 90 post non-myeloablative allogeneic transplant with allogeneic cytokine-induced killer (CIK) cells will be determined. FDC is defined as the attainment of \>95% donor type CD3+ cells. The outcome will be reported as number of participants who achieved full donor chimerism, a number without dispersion.

Secondary Outcome Measures

Name	Time	Method
Event-free Survival (EFS) Rate	2 years	Event-free Survival (EFS) rate will be assessed on all enrolled participants and is defined as the duration of time after cytokine-induced killer (CIK) cell infusion that the participants remain alive with experiencing relapse, Grade 3 to 4 acute graft vs host disease (aGVHD), or death. The outcome will be reported as the number of participants, stratified by receipt of CIK cells, that did not experience a specified event, a number without dispersion.
Overall Survival (OS)	2 years	Overall survival (OS) is an expression of the number of participants that remain alive 2 years after cytokine-induced killer (CIK) infusion. The outcome will be reported as the number of participants alive 2 years after CIK infusion, a number without dispersion.
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year	1 year	Acute graft vs host disease (aGvHD) Grade 2 to 4 was staged \& graded using modified Keystone criteria, as below. The outcome is reported as the number of participants that experience Grade 2 to 4 aGvHD within 100 days and 1 year. * Stage 1: Skin: rash \< 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea 500 to 1000 mL/day or persistent nausea with positive biopsy for GvHD * Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea 1000 to 1500 mL/day. * Stage 3: Skin: rash \> 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea \> 1500 mL/day. * Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin \> 15 mg/dL. Gut: severe abdominal pain with or without ileus Grade of aGvHD was determined as follows. * Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage * Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut * Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut * Grade 4: Stage 4 Skin + or Stage 2
Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands	Pre-transplant	Pre-transplant expression of natural-killer group 2, member D (NKG2D) ligands MIC A, MIC B, and the UL16 binding proteins (ULBPs) will be assessed in participants' bone marrow aspirates. The outcomes is expressed as the number of participants whose expression level for each ligand was elevated compared to background, represented by the known levels for individual without cancer.