T-cell Depleted Donor Lymphocyte Infusion (DLI)for Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National University Hospital, Singapore
Sponsor:
Collaborator:
Singapore General Hospital
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT00242515
First received: October 19, 2005
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

Primary Objectives:

This a pilot project to determine the feasibility of the preemptive CD8+ depleted T-cell donor lymphocyte infusion (DLI) in:

  • Reducing the incidence of graft versus host disease (GVHD) based on standard classification of acute and chronic GVHD
  • Improving hte disease remission rate in comparison with our previous study results.

Secondary Objectives:

  • To investigate the impact of CD8+ depleted T-cell DLI in hematopoietic chimerism, and immunologic recovery of transplant patients.

Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Procedure: CD8+ T-cell depleted donor lymphocyte infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preemptive CD8+ T-cell Depleted Donor Lymphocyte Infusion (DLI) Following Nonmyeloablative Stem Cell Transplantation (NMT) for Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • Incidence rate of acute and chronic GVHD
  • Disease remission rate post CD8+ depleted T-cell DLI

Secondary Outcome Measures:
  • Hematopoietic chimerism and immunologic recovery post CD8+ depleted T-cell DLI

Estimated Enrollment: 16
Study Start Date: March 2005
Estimated Study Completion Date: March 2008
Detailed Description:

The scientific investigation in this study protocol:

  1. Define the role of preemptive and specific DLI in preserving the GVL effect in the setting of NMT. The ability of selecting components of T cells for transplant and DLI will allow us to test the hypothesis of distinctive roles in subsets of T cells. It was found that CD8-depleted DLI was administered to prevent relapse after TCD (T-cell depleted) BMT (bone marrow as the stem cell source) or CD34-selected PBSC.

    Whether preemptive CD8-depleted DLI can perform this function after nonmyeloablative transplantation (NMT) needs to be established, as proposed in our study. If there turns out to be a role for DLI in these circumstances, a CD8-depleted lymphocyte product that can limit GVHD would be a very attractive option. We would also define the relationship of the level of donor chimerism and disease control.

  2. Investigate the impact of CD8-depleted DLI in NMT at specific doses and time points for the reduction of GVHD. The GVHD pattern may vary between different ethnic populations as suggested by our earlier NMT study. Our current proposed study will further shed light on the optimal GVHD prophylaxis regimen in the Singapore patient population.
  Eligibility

Ages Eligible for Study:   21 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed diagnosis of AML or high risk MDS in the following disease stages: Induction failure, first or subsequent remission, or untreated first relapse.
  2. Patient must have an HLA-compatible donor willing and capable of donating peripheral blood stem cells preferably or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated (HLA-compatible defined as 5/6 or 6/6 matched related or 6/6 molecular matched unrelated donor)
  3. Both patient and donor must sign written informed consent forms.
  4. Patients must have:

    • ECOG PS </= 2;
    • Ejective fraction > 40%;
    • DLCO > 40% of predicted;
    • Serum bilirubin </= 1.5x institutional upper limit of normal;
    • SGPT (ALT) and SGOT (AST) </= 2.5x institutional upper limit of normal;
    • Serum creatinine </= 2x upper limit of normal;
    • Creatinine clearance >/= 60mL/min. However, renal dysfunction is not an absolute contraindication for NMT as dialysis can be performed during NMT.

Exclusion Criteria:

  1. Not fulfilling any of the inclusion criteria
  2. Active life-threatening infection
  3. Overt untreated infection
  4. HIV positivity, hepatitis B or C antigen positivity with active hepatitis
  5. Pregnant or lactating women
  6. Donor contraindication (HIV seropositive confirmed by Western blot; hepatitis B antigenemia)
  7. Unable to donate bone marrow or peripheral blood due to concurrent medical condition
  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: NCT00242515

Contacts
Contact: Chien-Shing Chen, MD 67724613 mdcccs@nus.edu.sg

Locations
Singapore
Department of Hematology-Oncology, National University Hospital Recruiting
Singapore, Singapore, 119074
Sponsors and Collaborators
National University Hospital, Singapore
Singapore General Hospital
Investigators
Principal Investigator: Chien-Shing Chen, MD National University Hospital/National University Singapore
  More Information

No publications provided

Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT00242515     History of Changes
Other Study ID Numbers: TP02/28/04
Study First Received: October 19, 2005
Last Updated: January 7, 2014
Health Authority: Singapore: Health Sciences Authority

Keywords provided by National University Hospital, Singapore:
High risk Myelodysplastic Syndrome (MDS)

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

ClinicalTrials.gov processed this record on July 20, 2014