Partially HLA Mismatched (Haploidentical) Allogeneic Bone Marrow Transplantation

• Status: Terminated
• Trial end date: 2014-05-15
• Target enrollment: 0
• Participant gender: All

Summary

Allogeneic stem cell transplantation is a potentially curative treatment for patients with many hematologic malignancies (e.g. leukemia, lymphoma, and myeloma with high risk of relapse). This process requires a suitable donor. The best case scenario involves an Human Leukocyte Antigen (HLA) matched sibling donor. However, this type of donor is not always available. Donor registries can provide another source for matched unrelated donors, but this may take valuable time delaying treatment for the transplant recipient. Donor availability remains a significant barrier to the use of allogeneic (from a donor) stem cell transplant. This issue disproportionately affects patients of minority backgrounds. Novel strategies to improve outcomes using alternative donors are desperately needed.

Haploidentical transplants are an alternative which provides a readily available donor in the form of a partially HLA matched family member. This provides for more potential donors and the donors can be selected based on other factors that can play a role in transplant success (e.g. age, gender, KIR alloreactivity). Recent advances in transplant techniques have greatly improved success rates with haploidentical transplants although disease relapse has remained as issue.

This trial aims to provide an alternative transplant option for patients with hematologic malignancies who require bone marrow transplantation but lack an HLA identical donor. The investigational component of this study is the combination of the Fludarabine/ Busulfan/ Total Body Irradiation conditioning regimen and the HLA Haploidentical Transplant with post-transplant Cyclophosphamide.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Illinois at Chicago
• Treatments: Busulfan; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

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 following:

• 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 phase

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