Clinical trial NCT01341301
Conditions: Hematologic Malignancy
Keywords: allogeneic stem cell transplant TJU 2 Step HSCT Hematopoietic stem cell transplantation
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
Start date: 2010-05-01; Completion date: 2014-08-07
Enrollment: 25 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. In this research study, a way of strengthening the response of the donor cells against the disease has been developed. Patients will undergo one additional day between the two steps of the transplant which may allow their donor's cells to fight the disease more effectively.

Detailed description:
This is a phase II study in which patients receive a haploidentical HSCT from a single donor. The period between the donor lymphocyte infusion (DLI) and tolerizing doses of CY has been extended to allow for an increased period of allogeneic response against tumor targets. The outcomes of patients undergoing this extra time period will be compared to historical data to assess efficacy.

Primary Objective:

1\) To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach with an extra day inserted between the DLI and administration of cyclophosphamide (CY).

Secondary Objectives:

1. To assess the consistency and pace of engraftment.
2. To assess the pace of T cell and B cell immune recovery.
3. To assess regimen related toxicity, (GVHD) graft-versus-host disease incidence and severity, and overall survival in patients undergoing treatment on this protocol. .
4. To assess the tolerance of the period of fever, diarrhea, and rash in each arm in an effort to determine whether a longer interval prior to cytoxan changes this side effect qualitatively compared to prior patient groups or concurrent patient groups. N.B. Patients with hematologic malignancies in remission will continue to be transplanted without modification to the original 2-step approach and will serve as a concurrent comparison group.
5. To collect leukemia samples prior to transplant and after relapse whenever possible. To assess the overall degree of HLA-class I and class II expression on these paired samples. To test for loss of one or both HLA haplotypes in the relapsed tumor specimens.
6. To determine the number of cluster of differentiation 4 (CD4+) cluster of differentiation 25 (CD25+) FOXP3+ regulatory cells post HSCT and to assess whether this is correlated with the development of GVHD after transplant.

Arms: arm 1: CONDITIONING: Patients undergo Total Body Irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation 34 (CD34+) selected allogeneic HSCT on day 0

GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28.
Interventions: intervention 1: Total Body Irradiation intervention 2: Donor Lymphocyte Infusion (DLI) intervention 3: Cyclophosphamide intervention 4: Tacrolimus intervention 5: Mycophenolate mofetil intervention 6: Allogeneic hematopoietic stem cell transplantation intervention 7: Laboratory biomarker analysis
Intervention descriptions: intervention 1: Undergo TBI intervention 2: Undergo DLI intervention 3: Given IV intervention 4: Given IV or PO intervention 5: Given IV or PO intervention 6: Undergo allogeneic HSCT intervention 7: Correlative studies

Protocol documents: