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Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells: A Pilot Trial in Collaboration With the Massachusetts Institute of Technology

Phase 1/Phase 2
12 Years
60 Years
Open (Enrolling)
Acute Leukemia, Chronic Leukemia, Myelodysplastic Syndrome, Lymphoma, Myeloma

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Trial Information

Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells: A Pilot Trial in Collaboration With the Massachusetts Institute of Technology

1. Clinical transplantation of two cord blood units: one ex vivo expanded while another
unmanipulated unit to function as a back-up.

2. 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

- 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.

3. 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 GVHD and human leukocyte antigen (HLA) matching of MSC and recipient has
been shown to be not important. 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.

4. 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.

Inclusion Criteria:

- 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

1. Patients aged 12 years to 60 years.

2. Patient has no currently available HLA-A, B, C, DRB1 and DQB1 matched related or
unrelated donor.

3. 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))

- Treatment-related leukemia

- Induction failure

- CR1 with poor-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23

- 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

- 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

- > 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.

Exclusion Criteria:

1. 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%

2. Karnofsky score (adults) < 70% or Lansky score < 50% (pediatrics)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

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).

Outcome Time Frame:

1 month

Safety Issue:


Principal Investigator

William YK Hwang, MBBS, FRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Singapore General Hospital


Singapore: Health Sciences Authority

Study ID:




Start Date:

March 2012

Completion Date:

December 2013

Related Keywords:

  • Acute Leukemia
  • Chronic Leukemia
  • Myelodysplastic Syndrome
  • Lymphoma
  • Myeloma
  • Cord blood
  • unrelated donor
  • allogeneic
  • cell dose
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Chronic Disease