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Partially HLA Mismatched (Haploidentical) Allogeneic Bone Marrow Transplantation for Patients With Hematologic Malignancies

Phase 2
10 Years
75 Years
Open (Enrolling)
Hematologic Malignancies

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Trial Information

Partially HLA Mismatched (Haploidentical) Allogeneic Bone Marrow Transplantation for Patients With Hematologic Malignancies

Allogeneic stem cell transplantation is a potentially curative treatment for patients with
hematologic malignancies such as leukemia, lymphoma and myeloma who are at high risk of
relapse. As well as the potential to deliver high doses of chemotherapy or radiation this
procedure affords the benefit of an immunologic weapon against disease in the form of the
graft versus tumor effect.

The major variables affecting the outcome of allogeneic transplant include: patient
selection (age and comorbidities); disease status at the time of transplantation (remission
vs. active disease); type of donor (HLA matched vs. mismatched or related vs. unrelated);
type of conditioning regimen; source of stem cells (bone marrow vs. peripheral blood).
Recent advances in the field of stem cell transplant have substantially lowered transplant
related morbidity and mortality.

The availability of stem cell transplant as a treatment modality is dependent upon the
availability of a suitable donor. Best outcomes are thought to occur in HLA matched sibling
donors. The chance of a sibling being HLA matched is approximately 25%. Despite the
development of large worldwide donor registries the likelihood of finding an HLA matched
unrelated donor is 60-70% at best and drops to 10% in some ethnic minorities. In addition
the process of identifying, confirming and harvesting an unrelated donor is cumbersome and
time consuming at a time when the patient must proceed immediately to transplant (time from
initiation of search to identification of an unrelated donor identification takes a median
of 49 days). Therefore the development of alternative sources of hematopoietic stem cells is
an area of immense interest to many investigators.

Alternative sources include cord blood and HLA haploidentical donors. Cord blood has been an
attractive source permitting immediate availability and possibly a lower rate of graft
versus host disease (GVHD). However delay in engraftment, particularly after myeloablative
conditioning, remains a significant disadvantage. Haploidentical transplants carry some of
the same advantages with virtually all patients having immediate access to a suitable and
willing donor in the form of a partially HLA matched family member. Furthermore the number
of potential donors allows for donor selection based upon factors such as age, gender, KIR
alloreactivity. Finally the donor is readily available for future cellular therapies such as
donor lymphocyte infusion.

Early attempts at haploidentical transplantation were hampered by high rates of graft
failure and severe graft versus host disease. Recent advances in graft versus host disease
prophylaxis with post transplant high dose cyclophosphamide (Cy) have overcome these
barriers to a large degree. Published studies have shown that HLA-haploidentical bone marrow
transplant (BMT) after non-myeloablative conditioning and using 2 doses of
post-transplantation Cy followed by tacrolimus and mycophenolate mofetil (MMF) is a
well-tolerated procedure. However, the major cause of treatment failure in this high-risk
population was early relapse. As conditioning intensity has been clearly linked to rates of
relapse in multiple diseases, it is postulated that utilizing conditioning with higher
anti-tumor potential will lead to a lower relapse rate.

Given the advances in GVHD prophylaxis with post-transplantation Cy, reduced intensity
conditioning with Fludarabine, Busulfan and total body irradiation combined with high-dose
post-transplantation Cy is the platform for this study. The toxicities of this reduced
intensity conditioning regimen are not expected to differ substantially from previous data
incorporating post-transplantation Cy. However, this regimen may have higher anti-tumor
potential resulting in a decreased relapse rate.

Inclusion Criteria:

1. First-degree related donor or half-sibling who is at minimum HLA haploidentical

2. Lack of fully matched donor (related or unrelated). Patients with a matched unrelated
donor may only be enrolled if they require an urgent transplant. Urgency of
transplant will judged by PI and co-investigators.

3. Eligible diagnoses are listed below:

1. Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm that has progressed
during multiagent therapy including follicular lymphoma, Marginal zone (or MALT)
lymphoma, lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia, Hairy
cell leukemia, Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia
(CLL), Prolymphocytic leukemia, Multiple myeloma and Plasma cell leukemia

2. Poor-risk SLL or CLL

3. Aggressive lymphoma that has failed at least one prior regimen of multiagent
chemotherapy, and patient is either ineligible for autologous BMT or autologous
BMT is not recommended including Hodgkin lymphoma, high grade Follicular
lymphoma, Mantle cell lymphoma, Diffuse large B-cell lymphoma, Burkitt's
lymphoma/leukemia, Anaplastic large cell lymphoma, Plasmablastic lymphoma,
Peripheral T-cell lymphoma

4. Relapsed or refractory acute leukemias.

5. Poor-risk acute leukemia in first remission:

i. Acute myeloid leukemia (AML) with at least one of the following:

- AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative disorder

- Presence of FLT3 internal tandem duplications

- Poor-risk cytogenetics

ii. Acute lymphoblastic leukemia and/or lymphoma (ALL) with at least one of the

- Poor risk cytogenetics

- Primary refractory disease

iii. Biphenotypic leukemia

f. MDS with at least one of the following poor-risk features: i. Poor-risk
cytogenetics ii. Int-2 or high IPSS score iii. Treatment-related MDS iv. MDS
diagnosed before age 21 years v. Progression on or lack of response to standard
hypomethylator therapy vi. Life-threatening cytopenias

g. Imatinib-refractory chronic myelogenous leukemia (CML) in accelerated or chronic

h. Philadelphia chromosome negative myeloproliferative neoplasm

i. Chronic myelomonocytic leukemia

5. Adequate end-organ function as measured by:

1. Left ventricular ejection fraction ≥ 35%

2. Bilirubin ≤ 3.0 mg/dL and ALT and AST < 5 x ULN

3. FEV1 and FVC > 40% of predicted

6. Karnofsky score > 60

7. Lack of recipient anti-donor HLA antibody

Type of Study:


Study Design:

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

Outcome Measure:

Engraftment Rate

Outcome Description:

To estimate engraftment rates and incidence of full donor chimerism at Day 60 in patients undergoing an HLA haploidentical stem cell transplant with post transplant high dose cyclophosphamide.

Outcome Time Frame:

Up to Day 60 post-transplant.

Safety Issue:


Principal Investigator

Pritesh Patel, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Illinois


United States: Institutional Review Board

Study ID:




Start Date:

August 2012

Completion Date:

August 2023

Related Keywords:

  • Hematologic Malignancies
  • Neoplasms
  • Hematologic Neoplasms



University of Illinois Cancer CenterChicago, Illinois  60612-7243