Trial Outcomes & Findings for Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders (NCT NCT01392989)
NCT ID: NCT01392989
Last Updated: 2019-05-07
Results Overview
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.
COMPLETED
PHASE2
44 participants
90 days
2019-05-07
Participant Flow
Participant milestones
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
Total Lymphoid Irradiation (TLI)
STARTED
|
44
|
|
Total Lymphoid Irradiation (TLI)
COMPLETED
|
44
|
|
Total Lymphoid Irradiation (TLI)
NOT COMPLETED
|
0
|
|
CIK Cell Infusion
STARTED
|
31
|
|
CIK Cell Infusion
COMPLETED
|
31
|
|
CIK Cell Infusion
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
Baseline characteristics by cohort
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
n=44 Participants
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
22 Participants
n=5 Participants
|
|
Age, Continuous
|
63.9 Years
STANDARD_DEVIATION 6.58 • n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
41 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
39 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
44 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 90 daysPopulation: Cytokine-induced killer (CIK) cells were infused in a subset of participants.
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.
Outcome measures
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
n=31 Participants
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
Full Donor Chimerism (FDC)
|
6 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Cytokine-induced killer (CIK) cells were infused in a subset of participants. Participants that did not receive CIK cells were not included in this analysis.
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.
Outcome measures
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
n=31 Participants
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
Overall Survival (OS)
|
16 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: All participants are reported. Cytokine-induced killer (CIK) cells were infused in a subset of participants.
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.
Outcome measures
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
n=44 Participants
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
Event-free Survival (EFS) Rate
CIK-infused participants
|
14 Participants
|
|
Event-free Survival (EFS) Rate
Non-CIK-infused participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Cytokine-induced killer (CIK) cells were infused in a subset of participants. Results are reported for both subsets and collectively, at 2 time points.
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
Outcome measures
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
n=44 Participants
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
All participants within 100 days
|
9 Participants
|
|
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
All participants within 1 year
|
11 Participants
|
|
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
CIK-infused participants within 100 days
|
3 Participants
|
|
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
CIK-infused participants within 1 year
|
5 Participants
|
|
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
Non-CIK-infused participants within 100 days
|
6 Participants
|
|
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
Non-CIK-infused participants within 1 year
|
6 Participants
|
SECONDARY outcome
Timeframe: Pre-transplantPopulation: Insufficient tumor sample materials from the pre-transplant diagnostic bone marrow aspirate was available for the research analysis. No analysis was conducted.
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.
Outcome measures
Outcome data not reported
Adverse Events
Allogeneic Cytokine Induced Killer Cells (CIK)
Serious adverse events
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
n=44 participants at risk
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
General disorders
Fever
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Infections and infestations -Other, bacteremia
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
General disorders
Death NOS
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, progressive disease
|
40.9%
18/44 • Number of events 18 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, GvHD
|
6.8%
3/44 • Number of events 3 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration (Pneumonia)
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Sepsis
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Renal and urinary disorders
Renal and urinary disorders -Other, Renal failure
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Investigations
Lymphocyte count increased
|
2.3%
1/44 • Number of events 1 • 2 years
|
Other adverse events
| Measure |
Allogeneic Cytokine Induced Killer Cells (CIK)
n=44 participants at risk
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
CIK cells: Standard of care
Cyclosporine: 5 mg/kg, po
Mycophenolate Mofetil: 15 mg/kg, oral
Thymoglobulin: 7.5 mg/kg, IV
|
|---|---|
|
Immune system disorders
Serum sickness
|
29.5%
13/44 • Number of events 16 • 2 years
|
|
Blood and lymphatic system disorders
Hemolysis
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Cardiac disorders
Cardiac disorders - Other, cardiac bigeminy
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.8%
3/44 • Number of events 3 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.8%
3/44 • Number of events 3 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Buttock Pain
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Nervous system disorders
Headache
|
9.1%
4/44 • Number of events 6 • 2 years
|
|
Nervous system disorders
Dizziness
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Eye disorders
Blurred vision
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
General disorders
Chills
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
General disorders
Localized Edema
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
General disorders
Pain
|
2.3%
1/44 • Number of events 2 • 2 years
|
|
General disorders
Fever
|
20.5%
9/44 • Number of events 11 • 2 years
|
|
General disorders
Non-cardiac chest pain
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
General disorders
General Disorders Other - Peripheral Edema
|
6.8%
3/44 • Number of events 3 • 2 years
|
|
Gastrointestinal disorders
Abdominal pain
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Gastrointestinal disorders
Dyspepsia
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Dysphagia
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Gastric ulcer
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Mucositis oral
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders -Other, Diverticulitis
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Constipation
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
9.1%
4/44 • Number of events 4 • 2 years
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Otitis externa
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Lung infection
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Upper respiratory infection
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Bladder infection
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Urinary tract infection
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Infections and infestations - Other , Catheter Infection
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Infections and infestations
Infections and infestations - Other, Viremia
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Infections and infestations
Infections and infestations - Other, Coronavirus
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Investigations
Platelet Count decreased
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Investigations
Blood bilirubin increased
|
20.5%
9/44 • Number of events 9 • 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
4.5%
2/44 • Number of events 3 • 2 years
|
|
Investigations
Alanine aminotransferase increased
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Investigations
Weight Gain
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.8%
3/44 • Number of events 3 • 2 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Renal and urinary disorders
Acute kidney injury
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Renal and urinary disorders
Urinary frequency
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Renal and urinary disorders
Renal and urinary disorders -Other, Dysuria
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Reproductive system and breast disorders
Vaginal pain
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
6.8%
3/44 • Number of events 3 • 2 years
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
4.5%
2/44 • Number of events 2 • 2 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders Other, cutaneous eruptions
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders Other, Rash
|
11.4%
5/44 • Number of events 8 • 2 years
|
|
Vascular disorders
Hypertension
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Vascular disorders
Hematoma
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Vascular disorders
Thromboembolic event
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Vascular disorders
Vascular disorders - Other, DVT
|
2.3%
1/44 • Number of events 1 • 2 years
|
|
Psychiatric disorders
Psychiatric disorders - Other, altered mental status
|
2.3%
1/44 • Number of events 1 • 2 years
|
Additional Information
Everett Meyer, Assistant Professor of Medicine (Blood and Marrow Transplantation)
Stanford University
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place