Neural Tube DefectsPhase 2NCT01392989
Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
A Phase 2 study testing CIK cells, Cyclosporine and Mycophenolate Mofetil in people with Neural Tube Defects and Anemia, run by Everett Meyer at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Neural Tube Defects, Anemia, Leukemia, Myeloid
- What is being tested?
- CIK cells, Cyclosporine and Mycophenolate Mofetil
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to 19 Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
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
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.
Read the 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.
- Conditions
- Neural Tube Defects, Anemia, Leukemia, Myeloid, Bone Marrow Transplant Failure, Myelodysplastic Syndromes (MDS), Myeloproliferative Disorders
- Being tested
- CIK cells, Cyclosporine, Mycophenolate Mofetil, Thymoglobulin, Total Lymphoid Irradiation (TLI)
- Medical subject headings
- Neural Tube Defects, Anemia, Leukemia, Myeloid, Myelodysplastic Syndromes, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CIK cellsDrug
Also called Cytokine-induced Killer Cells
Standard of care
CyclosporineDrug
Also called cyclosporin, cyclosporin A
5 mg/kg, po
Also called MMF, CellCept
15 mg/kg, oral
ThymoglobulinDrug
Also called Anti-thymocyte globulin, ATG
7.5 mg/kg, IV
Total Lymphoid Irradiation (TLI)Radiation
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Cytokine-induced Killer Cells (CIK) | Experimental | Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells. Receives: Drug: CIK cells; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Drug: Thymoglobulin; Radiation: Total Lymphoid Irradiation (TLI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days
Secondary outcomes (4)
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.
Measured: 2 years
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.
Measured: 2 years
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
Measured: 1 year
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.
Measured: Pre-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2011 (estimated)
- Study startMar 2011
- Primary completion7 Jun 2016
- Study completion19 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neural Tube DefectsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Everett Meyer
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Everett Meyer, Stanford University
- Investigators
- Everett Meyer, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01392989
- Sponsor's protocol ID
- IRB-18127
- Other IDs
- SU-04202010-5724, BMT217
- Status last verified
- Apr 2019
- First submitted
- 21 Jun 2011
- Last updated
- 7 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30951840
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01392989
- Acronym / sponsor ID
- IRB-18127
- Conditions
- Neural Tube Defects, Anemia, Leukemia, Myeloid, Bone Marrow Transplant Failure, Myelodysplastic Syndromes (MDS), Myeloproliferative Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Everett MeyerUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- 7 Jun 2016 (actual)
- Study completion
- 19 Mar 2017 (actual)
- First posted
- 13 Jul 2011 (estimated)
- Results
- Posted 7 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Cytokine-induced Killer Cells (CIK) | Experimental | Drug: CIK cells, Drug: Cyclosporine, Drug: Mycophenolate Mofetil, Drug: Thymoglobulin, Radiation: Total Lymphoid Irradiation (TLI)Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CIK cellsAlso: Cytokine-induced Killer CellsStandard of care | Drug | Allogeneic Cytokine-induced Killer Cells (CIK) |
| CyclosporineAlso: cyclosporin, cyclosporin A5 mg/kg, po | Drug | Allogeneic Cytokine-induced Killer Cells (CIK) |
| Mycophenolate MofetilAlso: MMF, CellCept15 mg/kg, oral | Drug | Allogeneic Cytokine-induced Killer Cells (CIK) |
| ThymoglobulinAlso: Anti-thymocyte globulin, ATG7.5 mg/kg, IV | Drug | Allogeneic Cytokine-induced Killer Cells (CIK) |
| Total Lymphoid Irradiation (TLI) | Radiation | Allogeneic Cytokine-induced Killer Cells (CIK) |
Primary outcome
Full Donor Chimerism (FDC)
Time frame: 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.
4 secondary outcomes
Overall Survival (OS)
Time frame: 2 years
Event-free Survival (EFS) Rate
Time frame: 2 years
Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
Time frame: 1 year
Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands
Time frame: Pre-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30951840Narayan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Everett Meyer, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CIK cells, Cyclosporine and Mycophenolate Mofetil in people with Neural Tube Defects and Anemia, run by Everett Meyer at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Full Donor Chimerism (FDC) (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01392989, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2019.