A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies
6 Months
65 Years
Both
MDS, Leukemias, Lymphomas
Trial Information
A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies
Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or
nonmyeloablative conditioning, is a potentially curative treatment for a variety of
hematologic malignancies and non-malignant hematologic disorders. Of all the potential
sources of allografts, transplantation of stem cells from a human leukocyte antigen
(HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and
progression-free survival. Unfortunately, only about a third of candidates for alloBMT have
HLA-matched siblings.
For patients who lack HLA-matched siblings, there are three alternative sources of stem
cells for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially
HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA
haplotype with each biological parent or child and half of siblings, an eligible
haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical
BMT has been associated with significant risks of graft rejection and severe GVHD, which are
manifestations of excessive alloreactivity by host and donor T cells, respectively.
The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that
have been rigorously depleted of mature T cells or selectively depleted of alloreactive T
cells, but the risks of serious infection and death from prolonged immune compromise in
these patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive
antineoplastic agent that has an established role in conditioning for alloBMT.
Typically, the drug is administered prior to transplantation to prevent graft rejection by
suppressing the host immune system. However, pre-transplantation conditioning with Cy
increases the risk of GVHD following allogeneic T cell infusion in mouse models. In
contrast, administration of a properly timed, high dose of Cy after BMT inhibits both graft
rejection and GVHD.
Inclusion Criteria:
- Acute lymphocytic leukemia in high risk CR1
- Acute myeloid leukemia in CR1
- Therapy-related AML
- RAEB with >5% and <20% bone marrow blasts
- Chronic myelogenous leukemia beyond 1st chronic phase
- CMMoL
- JMML
- Chemotherapy-resistant Hodgkins Lymphoma or intermediate or high grade Non-Hodgkins
lymphoma (Less than a PR after standard or salvage chemotherapy)
- Mantle cell lymphoma: chemotherapy refractory (Less than a PR after standard or
salvage chemotherapy) or patients beyond CR1 with chemosensitive disease
- Follicular Lymphoma, Grade 3
- Transformed indolent lymphomas
Exclusion Criteria:
- Poor cardiac function: left ventricular ejection fraction <45% as determined by MUGA
or ECHO. For pediatric patients LVEF <45% or a shortening fraction below normal
limits for age.
- Poor pulmonary function: FEV1 and FVC <50% predicted for patients who have not
received thoracic or mantle irradiation. For patients who have received thoracic or
mantle irradiation, FEV1 and FVC <70% predicted or DLCO < 50 of predicted. For
children unable to perform PFTs because of developmental stage pulse oximetry < 85%
on RA
- Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary
malignancy)
- Poor renal function: Creatinine >2.0mg/dl or creatinine clearance
- HIV-positive
- Positive leukocytotoxic crossmatch
- Women of childbearing potential who currently are pregnant or who are not practicing
adequate contraception
- Uncontrolled viral, bacterial, or fungal infections Patients with symptoms consistent
with RSV, influenza A, B, or parainfluenza at the time of enrollment will be assayed
for the above viruses and if positive are not eligible for the trial until they are
no longer symptomatic (patients may have continued assay positivity for a period of
time post resolution of symptoms secondary to the nature of the assay.
- Indolent lymphomas (Follicular Grade 1 and 2, marginal zone, chronic lymphocytic
leukemia, small lymphocytic lymphoma, MALT)
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening
Outcome Measure:
To estimate the incidence of donor cell engraftment following myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies.
Outcome Time Frame:
Day 14-60
Safety Issue:
Yes
Principal Investigator
Heather Symons, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Johns Hopkins University
Authority:
United States: Institutional Review Board
Study ID:
J0820
NCT ID:
NCT00796562
Start Date:
November 2008
Completion Date:
December 2013
Related Keywords:
- MDS
- Leukemias
- Lymphomas
- Leukemia
- Lymphoma
- Hematologic malignancies
- ALL
- AML
- MDS
- Transplantation
- Mismatched
- Haploidentical
- Busulfan
- Cyclophosphamide
- Cellcept
- Tacrolimus
- TBI
- CMMOL
- CML
- JMML
- Leukemia
- Lymphoma
- Hematologic Neoplasms
Name | Location |
|---|---|
| The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231 |
| Sidney Kimmel Comprehensive Cancer Center | Lutherville, Maryland |
