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Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Matched Unrelated Double Cord Blood Transplant for the Treatment of Leukemias, Lymphomas, and Pre-Malignant Blood Disorders


Phase 1
18 Years
69 Years
Not Enrolling
Both
Leukemia, Non-Hodgkins Lymphoma, Hodgkins Lymphoma, MDS, Multiple Myeloma

Thank you

Trial Information

Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Matched Unrelated Double Cord Blood Transplant for the Treatment of Leukemias, Lymphomas, and Pre-Malignant Blood Disorders


Background:

The major limitations of umbilical cord blood transplantation (UCBT) in adults are graft
rejection and delayed engraftment leading to increased infection-related morbidity and
treatment related mortality (TRM). To increase engraftment rates while at the same time
enhancing graft-versus-tumor effect, previous studies within our institution have employed
the strategy of targeted immune depletion (TID). The goal of TID is to use T-cell
suppressive chemotherapy prior to the conditioning regimen to treat the patient's disease
while concurrently depleting host T-cells. This has lead to earlier complete donor chimerism
in the setting of allogeneic sibling donor and matched unrelated donor transplantation. Our
aim in the current protocol is to extend the strategy of TID to reduced-intensity UCBT, with
the goal of more rapid engraftment, leading to decreased TRM and increased overall survival.
Our intention is to investigate this approach in the setting of double cord blood transplant
in adults in a pilot manner.

Objectives:

- The primary objective of this study is to see whether targeted immune depletion can
shorten the time to neutrophil recovery and improve the cord blood engraftment rate as
measured by ANC greater than or equal to 500 x 3 and at least partial donor chimerism
(10-90%).

- Secondary objectives include further assessment of hematopoetic recovery, treatment
related morbidity including infections and acute and chronic GVHD, TRM, progression
free and overall survival, further assessment of immune reconstitution, and study of
engraftment kinetics as they apply to prediction of which of the two transplanted cords
will engraft in relation to cell dose, CD34+ dose, HLA-match, and other experimental
variables.

Eligibility:

- Adults (18-69 years) with advanced or high-risk hematologic malignancies including AML,
ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPD who lack a readily available
HLA-matched sibling or greater than or equal to 7/8 HLA-matched unrelated donor.
Patients must have life expectancy of at least 3 months, ECOG less than or equal to 2,
and relatively normal major organ functions.

- Patients must have two partially HLA-matched UCB units. Units must be HLA-matched at
HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution
molecular typing) 4-6/6 with the recipient and 4-6/6 with each other. Each unit must
contain a minimum precryopreserved, nucleated cell dose of 1.5 x 10(7) per kilogram.

Design:

- This is a Pilot study of TID in the setting of reduced-intensity double cord blood
transplant in adults.

- Patients will receive disease-specific induction chemotherapy (EPOCH-F/R or FLAG) prior
to transplant for disease control and immune depletion.

- All patients will receive an identical conditioning regimen consisting of
cyclophosphamide 1200 mg/m(2)/day IV for 4 days and fludarabine 30 mg/m(2)/day for 4
days.

- A maximum of 13 patients will be transplanted in the initial part of this pilot study.
If no stopping rules are reached, the study will be expanded to allow the
transplantation of an additional 12 patients (a total of 25 patients).

Inclusion Criteria


- ELIGIBILITY CRITERIA:

- Adults (18-69 years) with advanced or high-risk hematologic malignancies including
AML, ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPD who lack a readily
available HLA-matched sibling or greater than or equal to 7/8 HLA-matched unrelated
donor. Patients must have life expectancy of at least 3 months, ECOG less than or
equal to 2, and relatively normal major organ functions.

- Patients must have two partially HLA-matched UCB units. Units must be HLA-matched at
HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution
molecular typing) 4-6/6 with the recipient and 4-6/6 with each other. Each unit must
contain a minimum precryopreserved, nucleated cell dose of 1.5 x 10(7) per kilogram.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

The primary objective of this study is to see whether targeted immune depletion can shorten the time to hematopoietic recovery and improve cord blood engraftment rate as measured by ANC greater than 500 X 3 and at least partial donor chimerism (...

Principal Investigator

William L Dahut, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

090210

NCT ID:

NCT00973804

Start Date:

August 2009

Completion Date:

August 2014

Related Keywords:

  • Leukemia
  • Non-Hodgkins Lymphoma
  • Hodgkins Lymphoma
  • MDS
  • Multiple Myeloma
  • Reduced Intensity Conditioning
  • Umbilical Cord Blood Transplant
  • Targeted Immune Depletion
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Non-Hodgkins Lymphoma
  • Hodgkins Lymphoma
  • Hematologic Diseases
  • Hodgkin Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Precancerous Conditions

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892