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

Anemia Clinical Trial

Official title:

Post Transplant Infusion of Allogeneic Cytokine Induced Killer Cells as Consolidative Therapy After Non-Myeloablative Allogeneic Transplantation in Patients With Myelodysplasia or Myeloproliferative Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01392989
• Other study ID #: IRB-18127
• Secondary ID: SU-04202010-5724
• Status: Completed
• Phase: Phase 2
• Start date: March 2011
• Est. completion date: March 19, 2017

Study information

• Verified date: April 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: March 19, 2017
• Est. primary completion date: June 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

INCLUSION CRITERIA, RECIPIENT WITH MYELODYSPLASTIC SYNDROME (MDS)

• Diagnosis of MDS classifiable by the World Health Organization (WHO) on the basis of:

• Refractory anemia

• Refractory anemia with excess blasts-1

• Refractory anemia with excess blasts-2

• Refractory cytopenia with multi-lineage dysplasia

• Refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts

• Chronic myelomonocytic leukemia (CMML)

• MDS transformed to acute leukemia

• MDS-unclassified

• Participants with advanced MDS must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow examination within 1 month prior.

• Participants with evolution to acute leukemia (AML) must be in a morphologic leukemia free-state (MLFS) with blasts < 5%

INCLUSION CRITERIA, RECIPIENT WITH MYELOPROLIFERATIVE DISORDER (MPD)

• Diagnosis of MPD on the basis of:

• Idiopathic myelofibrosis

• Polycythemia vera

• Essential thrombocythemia

• Chronic myelomonocytic leukemia (CML)

• CML, Philadelphia chromosome-negative

• Chronic neutrophilic leukemia

• Chronic eosinophilic leukemia

• Hypereosinophilic cyndrome

• Systemic mastocytosis

• < 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow examination within 1 month prior.

• Participants with evolution to acute leukemia (AML) must be in a morphologic leukemia free-state (MLFS) with blasts < 5%. Presence of residual dysplastic features following cytoreductive therapy is acceptable.

INCLUSION CRITERIA, RECIPIENT WITH THERAPY-RELATED MYELOID NEOPLASM (t MDS)

• < 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow examination within 1 month prior.

• Morphologic leukemia free-state with blasts < 5 %.

• Age > 50 years, or < 50 years of age but at high-risk for regimen-related toxicity associated with conventional myeloablative transplants due to pre-existing medical conditions or prior therapy

• Availability of a fully HLA-matched or single antigen/allele mismatched sibling or unrelated donor

• Prior malignancy diagnosed > 5 years ago without evidence of disease, or < 5 years ago with life expectancy of > 5 years are eligible (prior malignancy is not a requirement)

INCLUSION CRITERIA, DONOR

• Donors must be HLA-matched or one allele mismatched.

• Donor age < 75 (EXCEPTION by Principal Investigator discretion)

• Must consent to PBSC mobilization with G-CSF; apheresis; and collection and donation of plasma

• Donor must consent to placement of a central venous catheter in the event that peripheral venous access is limited.

EXCLUSION CRITERIA, RECIPIENT

Any of the following:

• Uncontrolled CNS involvement with disease

• Pregnant

• Cardiac function: ejection fraction (EF) < 35% or uncontrolled cardiac failure

• Diffusing capacity of the lungs for carbon monoxide (DLCO) < 40% predicted

• Bilirubin > 3 mg/dL

• Aspartate aminotransferase (AST) > 3x the upper limit of normal (ULN)

• Alanine aminotransferase (ALT) > 3x ULN

• Estimated creatinine clearance < 50 mL/min

• Karnofsky performance score (KPS) < 70%

• Documented fungal disease that is progressive despite treatment

• HIV-positive

EXCLUSION CRITERIA, DONOR

Any of the following:

• Identical twin to recipient

• Pregnant or lactating

• Prior malignancy within the preceding 5 years (EXCEPTION: non-melanoma skin cancers)

• HIV seropositivity

Related Conditions & MeSH terms

• Anemia
• Bone Marrow Transplant Failure
• Disease
• Leukemia, Myeloid
• Myelodysplastic Syndromes
• Myelodysplastic Syndromes (MDS)
• Myeloproliferative Disorders
• Neural Tube Defects
• Preleukemia
• Spinal Dysraphism
• Syndrome

Intervention

Drug:
• CIK cells
Standard of care
• Cyclosporine
5 mg/kg, po
• Mycophenolate Mofetil
15 mg/kg, oral
• Thymoglobulin
7.5 mg/kg, IV

Radiation:
• Total Lymphoid Irradiation (TLI)

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Everett Meyer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Full Donor Chimerism (FDC)	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.	90 days
Secondary	Overall Survival (OS)	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.	2 years
Secondary	Event-free Survival (EFS) Rate	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.	2 years
Secondary	Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 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	1 year
Secondary	Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands	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.	Pre-transplant