A Study of Bone Marrow Transplantation Using Fully-Matched Relatives as Donors for Patients With Hematological Malignancies

Phase 2

Completed

Conditions: Leukemia
Multiple Myeloma
Hodgkin's Disease
Lymphoma
Hematological Malignancies

Brief Summary: This research study uses a drug called cyclophosphamide to decrease the incidence of GVHD in matched sibling hematopoietic stem cell transplant. In doing so, the goal of the study is to increase overall survival.

Detailed Description: This research protocol has been developed for patients undergoing matched-sibling hematopoietic stem cell transplant (HSCT). The patients who are treated according to this 2 step allogeneic HSCT protocol will receive cyclophosphamide to induce in-vivo tolerization of both autologous and allogeneic lymphocytes, followed by an allogeneic CD34-selected HSCT. The primary research questions relate to immune reconstitution, incidence of GVHD, and relapse in patients who receive lymphocyte treatment of this type in allogeneic HSCT and how it impacts overall survival.

Recruitment & Eligibility

Inclusion Criteria

Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients will be considered high-risk if they have any of the following:
1. Age > 50 years
2. ECOG Performance status of <2
3. Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st CR; second or greater CR, 1st relapse; any ph+ ALL
4. CML 2nd chronic phase, accelerated phase, or blastic phase
5. MDS with IPS of Intermediate 2 or greater
6. Any myeloproliferative disorder
7. Hodgkin lymphoma: relapsed, refractory, or primary induction failure
8. Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT
9. Other conditions not listed will be assessed as high-risk by the PI
Patients must have a related donor who is either HLA-identical or a one antigen mismatch at the HLA- A; B; C; and DR loci.
Patients must adequate organ function:
1. LVEF of >45%
2. DLCO (adjusted for hemoglobin) >45% of predicted
3. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
4. Creatinine clearance of > 60 ml/min
Patients must be willing to use contraception if they have childbearing potential
Able to give informed consent

Exclusion Criteria

ECOG performance status of 3 or 4.
HIV positive
Active involvement of the central nervous system with malignancy
Psychiatric disorder that would preclude patients from signing an informed consent
Pregnancy
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.

Arm && Interventions

Group	Intervention	Description
Allogeneic Transplantation	Matched Sibling Allogeneic Transplantation	Matched Sibling Allogeneic Transplantation

Primary Outcome Measures

Name	Time	Method
Number of Patients With Overall Survival	1 Year after transplant	The primary objective of this prospective, phase II trial was to obtain an OS rate of \>60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The \>60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol.

Secondary Outcome Measures