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Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Singapore General Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Whitehead Institute for Biomedical Research
Blood Services Group, Health Sciences Authority of Singapore
Information provided by (Responsible Party):
Singapore General Hospital
ClinicalTrials.gov Identifier:
NCT01624701
First received: March 20, 2012
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Acute Leukemia
Chronic Leukemia
Myelodysplastic Syndrome
Lymphoma
Myeloma
Other: Ex vivo expanded cord blood cells
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Singapore General Hospital:

Primary Outcome Measures:
  • Safety [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Engraftment [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Neutrophil engraftment (ANC>500/ul) in subjects as demonstrated by number of subjects with engraftment <=21 days.


Estimated Enrollment: 10
Study Start Date: March 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Ex vivo expanded cord blood cells
    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.
Detailed Description:
  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 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.
  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.
  Eligibility

Ages Eligible for Study:   12 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 etc)
    • 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.

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624701

Contacts
Contact: William YK Hwang, MBBS, FRCP +65 63214625 william.hwang.y.k@sgh.com.sg
Contact: Yvonne SM Loh, MBBS, MRCP +65 63214855 yvonne.loh.s.m@sgh.com.sg

Locations
Singapore
Singapore General Hospital Recruiting
Singapore, Singapore, 169608
Contact: William YK Hwang, MBBS, FRCP    +65 63214625    william.hwang.y.k@sgh.com.sg   
Contact: Yvonne SM Loh, MBBS, MRCP    +65 63214855    yvonne.loh.s.m@sgh.com.sg   
Principal Investigator: William YK Hwang, MBBS, FRCP         
Sub-Investigator: Yeow T Goh, MBBS, MMed         
Sub-Investigator: Yeh C Linn, MBBS         
Sub-Investigator: Yvonne SM Loh, MBBS, MRCP         
Sub-Investigator: Xiubo Fan, PhD         
Sub-Investigator: Pak Y Chu, PhD         
Sub-Investigator: Aloysius Ho, MBBS, FRCP         
Sub-Investigator: Colin P Diong, MBBS, MRCP         
Sub-Investigator: Mickey BC Koh, MBBS, FRCPath         
Sponsors and Collaborators
Singapore General Hospital
Whitehead Institute for Biomedical Research
Blood Services Group, Health Sciences Authority of Singapore
Investigators
Principal Investigator: William YK Hwang, MBBS, FRCP Singapore General Hospital
  More Information

No publications provided

Responsible Party: Singapore General Hospital
ClinicalTrials.gov Identifier: NCT01624701     History of Changes
Other Study ID Numbers: 2009/925/B
Study First Received: March 20, 2012
Last Updated: June 20, 2012
Health Authority: Singapore: Health Sciences Authority

Keywords provided by Singapore General Hospital:
Cord blood
unrelated donor
allogeneic
cell dose

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions

ClinicalTrials.gov processed this record on November 20, 2014