Back to resultsPost T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
Primary Purpose
Neural Tube Defects, Anemia, Leukemia, Myeloid
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CIK cells
Cyclosporine
Mycophenolate Mofetil
Thymoglobulin
Total Lymphoid Irradiation (TLI)
Sponsored by
About this trial
This is an interventional treatment trial for Neural Tube Defects
Eligibility Criteria
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
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Allogeneic Cytokine-induced Killer Cells (CIK)
Arm Description
Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01392989
Brief Title
Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
June 7, 2016 (Actual)
Study Completion Date
March 19, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Everett Meyer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neural Tube Defects, Anemia, Leukemia, Myeloid, Bone Marrow Transplant Failure, Myelodysplastic Syndromes (MDS), Myeloproliferative Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Allogeneic Cytokine-induced Killer Cells (CIK)
Arm Type
Experimental
Arm Description
Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.
Intervention Type
Drug
Intervention Name(s)
CIK cells
Other Intervention Name(s)
Cytokine-induced Killer Cells
Intervention Description
Standard of care
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
cyclosporin, cyclosporin A
Intervention Description
5 mg/kg, po
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
MMF, CellCept
Intervention Description
15 mg/kg, oral
Intervention Type
Drug
Intervention Name(s)
Thymoglobulin
Other Intervention Name(s)
Anti-thymocyte globulin, ATG
Intervention Description
7.5 mg/kg, IV
Intervention Type
Radiation
Intervention Name(s)
Total Lymphoid Irradiation (TLI)
Primary Outcome Measure Information:
Title
Full Donor Chimerism (FDC)
Description
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.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
2 years
Title
Event-free Survival (EFS) Rate
Description
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.
Time Frame
2 years
Title
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
Description
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
Time Frame
1 year
Title
Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands
Description
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.
Time Frame
Pre-transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Everett Meyer, MD, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30951840
Citation
Narayan R, Benjamin JE, Shah O, Tian L, Tate K, Armstrong R, Xie BJ, Lowsky R, Laport G, Negrin RS, Meyer EH. Donor-Derived Cytokine-Induced Killer Cell Infusion as Consolidation after Nonmyeloablative Allogeneic Transplantation for Myeloid Neoplasms. Biol Blood Marrow Transplant. 2019 Jul;25(7):1293-1303. doi: 10.1016/j.bbmt.2019.03.027. Epub 2019 Apr 3.
Results Reference
derived
Learn more about this trial
Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
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