Acute LeukemiaPhase 1/2NCT01624701
Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells
A Phase 1/2 study testing Ex vivo expanded cord blood cells in people with Acute Leukemia and Chronic Leukemia, run by Singapore General Hospital at 1 site in Singapore.
Trial summary
This is a pilot clinical trial to assess the feasibility and efficacy of expanding umbilical cord blood derived blood stem cells for transplantation using a combination of chemical factors and stromal co-culture. Bone marrow (BM) mesenchymal stromal cells (MSC) will be obtained from a separate bone marrow donor. Read more about this study
- Who is it for?
- Ages 12 to 60 years
- Conditions the study is for
- Acute Leukemia, Chronic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Ex vivo expanded cord blood cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteSingapore
- Study dates
- Mar 2012to Jul 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 12 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients will be from the Department of Haematology, Singapore General Hospital, who have the diagnoses listed below and who meet the inclusion criteria. They have to be deemed suitable for trial by the respective attending doctor as well as a panel of at least three hematologists. Suitability will be reassessed by the Principal Investigator again
- Patients aged 12 years to 60 years.
- Patient has no currently available HLA-A, B, C, DRB1 and DQB1 matched related or unrelated donor.
- Patient must have a hematologic malignancy requiring allogeneic haematopoietic stem cell transplantation as further defined below (from National Marrow Donor Program and American Society of Blood and Marrow Transplantation Guidelines) and as further agreed upon by a panel of at least three hematologists specializing in transplantation.
- Acute myelogenous leukemia (AML): High-risk AML including:
- Antecedent hematological disease (e.g., myelodysplasia (MDS))
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- Treatment-related leukemia
- Induction failure
- 1st complete remission (CR1) with poor-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23 etc)
- 2nd complete remission (CR2) and beyond
- Acute lymphoblastic leukemia (ALL)
- CR1 up to age 35
- High-risk over age 35 including:
- Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23 rearrangements)
- High white cell count (> 30,000/mm3) at diagnosis
- CNS or testicular leukemia
- No CR within 4 weeks of initial treatment
- Induction failure
- CR2 and beyond
- Myelodysplastic syndromes (MDS)
- Intermediate-1 (INT-1), intermediate-2 (INT-2) or high IPSS score which includes:
- > 5% marrow blasts
- Other than good risk cytogenetics (not 5q- or normal)
- > 1 lineage cytopenia
- Chronic myelogenous leukemia (CML)
- Disease progression
- Accelerated phase
- Blast crisis (myeloid or lymphoid)
- Follicular lymphoma
- Poor response to initial treatment
- After second or subsequent relapse
- Transformation to diffuse large B-cell lymphoma
- Aggressive T-cell or B-Cell lymphoma
- After second or subsequent relapse
- No CR with initial treatment
- Mantle Cell: After second or subsequent relapse
- Hodgkin's lymphoma
- No initial CR
- After second or subsequent relapse
- Multiple myeloma: Patients failing autologous transplantation with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L may be considered for this protocol after initial therapy.
Who cannot join
- Inadequate Organ Function as defined by:
- Renal: Creatinine clearance > 60ml/min
- Hepatic: Bilirubin, AST/ALT < 2x upper limit of normal
- Pulmonary function: DLCOcorr > 50% normal
- Cardiac: left ventricular ejection fraction > 45%
- Karnofsky score (adults) < 70% or Lansky score < 50% (pediatrics)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells: A Pilot Trial in Collaboration With the Massachusetts Institute of Technology
This is a pilot clinical trial to assess the feasibility and efficacy of expanding umbilical cord blood derived blood stem cells for transplantation using a combination of chemical factors and stromal co-culture. Bone marrow (BM) mesenchymal stromal cells (MSC) will be obtained from a separate bone marrow donor. One cord blood unit will be expanded by this method while another cord blood unit will be infused without manipulation. The expanded cord blood unit will help boost the initial recovery of blood counts after transplantation, though it is expected that the unexpanded cord blood unit will provide the cells which will lead to long term engraftment of blood stem cells. A third cord blood unit will be identified for standby should the cord blood unit expansion fail.
Read the detailed description
- Clinical transplantation of two cord blood units: one ex vivo expanded while another unmanipulated unit to function as a back-up.
- Ten patients will be selected from those for whom:
- Allogeneic haematopoietic stem cell transplant is indicated (see details)
- No matched sibling or matched unrelated donor is available quickly enough for the transplant (no fully matched donor found within 1 month of initiation of donor search or donor found but not available for donation within 3 months of donor search).
- At least three unrelated donor cord blood unit can be identified with less than 2 antigens mismatches with the patient but with insufficient cell dose to meet the patient's requirements. If clinical efficacy of this protocol is demonstrated, we will proceed to a multicentre clinical trial with more patients.
- The investigators will obtain haplo-identical MSC from the bone marrow of sibling/parent/offspring of the patient. Although there will be some MSC co-infused with the cord blood cells, this has been shown to be safe in trials of MSC given for patients with graft versus host disease (GVHD) and human leukocyte antigen (HLA) matching of MSC and recipient has been shown to be not important. bone marrow mesenchymal stroma cells (BM-MSCs) derived from related donor bone marrow with a minimum of 2/6 HLA match have been safe for use in patients.1 If the haplo-identical MSC donor is not available, matched unrelated donor MSC would also be used.
- Efficacy will be assessed by the following and compared to published literature as well as historical controls:
- Neutrophil and platelet engraftment
- Post transplant 100-day mortality
- Overall and progression-free survival If clinical efficacy of this protocol is demonstrated, the investigators will proceed to a multicentre clinical trial with more patients.
- Conditions
- Acute Leukemia, Chronic Leukemia, Myelodysplastic Syndrome, Lymphoma, Myeloma
- Being tested
- Ex vivo expanded cord blood cells
- Keywords
- Cord blood, unrelated donor, allogeneic, cell dose
- Medical subject headings
- Myelodysplastic Syndromes, Lymphoma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ex vivo expanded cord blood cellsOther
Cord blood cells will be expanded ex vivo using a combination of stem cell factor (SCF), thrombopoietin (TPO), Flt3 ligand and IGFBP2 with mesenchymal stromal cell (MSC) co-culture.
| Study group | Role | What they receive |
|---|---|---|
| Expanded | Experimental | 'Ex vivo expanded cord blood cells Receives: Other: Ex vivo expanded cord blood cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Number of subjects with infusional toxicities (including fever, renal dysfunction within 72 hours of infusion) and potential immunologic competition (absent chimerism of donor cells by 21 days post transplantation).
Measured: 1 month
Secondary outcomes (1)
Engraftment
Neutrophil engraftment (ANC>500/ul) in subjects as demonstrated by number of subjects with engraftment <=21 days.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2012 (estimated)
- Study startMar 2012
- Primary completionJul 2015
- Study completionJul 2016 (estimated)
Why it stopped: Funding expired
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute LeukemiaStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Whitehead Institute for Biomedical Research, Blood Services Group, Health Sciences Authority of Singapore
- Responsible party
- Sponsor
- Investigators
- William YK Hwang, MBBS, FRCP, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01624701
- Sponsor's protocol ID
- 2009/925/B
- Status last verified
- Nov 2015
- First submitted
- 20 Mar 2012
- Last updated
- 30 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells: A Pilot Trial in Collaboration With the Massachusetts Institute of Technology
- ClinicalTrials.gov ID
- NCT01624701
- Acronym / sponsor ID
- 2009/925/B
- Conditions
- Acute Leukemia, Chronic Leukemia, Myelodysplastic Syndrome, Lymphoma, Myeloma
- Keywords
- Cord blood, unrelated donor, allogeneic, cell dose
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding expired
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- Whitehead Institute for Biomedical Research, Blood Services Group, Health Sciences Authority of Singapore
- Study start
- Mar 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2016 (estimated)
- First posted
- 21 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot clinical trial to assess the feasibility and efficacy of expanding umbilical cord blood derived blood stem cells for transplantation using a combination of chemical factors and stromal co-culture. Bone marrow (BM) mesenchymal stromal cells (MSC) will be obtained from a separate bone marrow donor. One cord blood unit will be expanded by this method while another cord blood unit will be infused without manipulation. The expanded cord blood unit will help boost the initial recovery of blood counts after transplantation, though it is expected that the unexpanded cord blood unit will provide the cells which will lead to long term engraftment of blood stem cells. A third cord blood unit will be identified for standby should the cord blood unit expansion fail.
Detailed description
- Clinical transplantation of two cord blood units: one ex vivo expanded while another unmanipulated unit to function as a back-up.
- Ten patients will be selected from those for whom:
- Allogeneic haematopoietic stem cell transplant is indicated (see details)
- No matched sibling or matched unrelated donor is available quickly enough for the transplant (no fully matched donor found within 1 month of initiation of donor search or donor found but not available for donation within 3 months of donor search).
- At least three unrelated donor cord blood unit can be identified with less than 2 antigens mismatches with the patient but with insufficient cell dose to meet the patient's requirements. If clinical efficacy of this protocol is demonstrated, we will proceed to a multicentre clinical trial with more patients.
- The investigators will obtain haplo-identical MSC from the bone marrow of sibling/parent/offspring of the patient. Although there will be some MSC co-infused with the cord blood cells, this has been shown to be safe in trials of MSC given for patients with graft versus host disease (GVHD) and human leukocyte antigen (HLA) matching of MSC and recipient has been shown to be not important. bone marrow mesenchymal stroma cells (BM-MSCs) derived from related donor bone marrow with a minimum of 2/6 HLA match have been safe for use in patients.1 If the haplo-identical MSC donor is not available, matched unrelated donor MSC would also be used.
- Efficacy will be assessed by the following and compared to published literature as well as historical controls:
- Neutrophil and platelet engraftment
- Post transplant 100-day mortality
- Overall and progression-free survival If clinical efficacy of this protocol is demonstrated, the investigators will proceed to a multicentre clinical trial with more patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Expanded | Experimental | Other: Ex vivo expanded cord blood cells'Ex vivo expanded cord blood cells |
Who may qualify
- Ages
- 12 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (40 listed)
- Patients will be from the Department of Haematology, Singapore General Hospital, who have the diagnoses listed below and who meet the inclusion criteria. They have to be deemed suitable for trial by the respective attending doctor as well as a panel of at least three hematologists. Suitability will be reassessed by the Principal Investigator again
- Acute myelogenous leukemia (AML): High-risk AML including:
- Acute lymphoblastic leukemia (ALL)
- Myelodysplastic syndromes (MDS)
- Chronic myelogenous leukemia (CML)
Key exclusion criteria (6 listed)
- Inadequate Organ Function as defined by:
- Karnofsky score (adults) < 70% or Lansky score < 50% (pediatrics)
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 |
|---|---|---|
| Ex vivo expanded cord blood cellsCord blood cells will be expanded ex vivo using a combination of stem cell factor (SCF), thrombopoietin (TPO), Flt3 ligand and IGFBP2 with mesenchymal stromal cell (MSC) co-culture. | Other | Expanded |
Primary outcome
Safety
Time frame: 1 month
Number of subjects with infusional toxicities (including fever, renal dysfunction within 72 hours of infusion) and potential immunologic competition (absent chimerism of donor cells by 21 days post transplantation).
1 secondary outcome
Engraftment
Time frame: 2 months
Results and safety
The study was stopped early (reason given: Funding expired). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2015.
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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.
William YK Hwang, MBBS, FRCP principal investigator
Singapore General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ex vivo expanded cord blood cells in people with Acute Leukemia and Chronic Leukemia, run by Singapore General Hospital at 1 site in Singapore.
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 40 inclusion and 6 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: stopped early, as of the sponsor's last update on 30 Nov 2015. 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 Singapore. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was stopped early (reason given: Funding expired). Results are not available in the source record.
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?
Safety (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Nov 2015.