Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplantation

David Rizzieri, MD1 site in 1 country264 target enrollmentFebruary 2008

Overview

Brief Summary

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free, and overall survival rates in patients treated with alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.

Detailed Description

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing. The study population is HIV negative, adult patients who are not pregnant but have confirmed diagnosis of disease; must have Cancer and Leukemia Group B (CALGB) performance status (PS) 0, 1, or 2; must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched unrelated donor who is evaluated and deemed able to provide peripheral blood stem cells (PBPCs) and/or marrow by the transplant team. The target population of patients is those with a high chance of progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.

Registry

clinicaltrials.gov

Start Date

February 2008

End Date

November 2013

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

David Rizzieri, MD

Responsible Party

Sponsor Investigator

Principal Investigator

David Rizzieri, MD

Associate Professor of Medicine

Duke University

Eligibility Criteria

Inclusion Criteria

•Subjects must have their diagnosis confirmed at the transplant center.
•Performance status must be Cancer and Leukemia Group B (CALGB) = 0, 1, or
•Subjects must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 or better allele level match matched unrelated donor (MUD) (at A,B, C, DRB1, DQ).
•HIV negative.
•Women of child bearing potential must have a negative pregnancy test within 1 week of starting therapy.
•Subjects \> or equal to 18 years of age are eligible.
•Subjects must have a Multi Gated Acquisition Scan (MUGA) and/or Echocardiography (ECHO) or cardiac magnetic resonance (MR) and or diffusing capacity testing of the lung for carbon monoxide (DLCO) performed before transplant.
•Specific populations:
•Group A) Subjects with a high chance of progressive lymphoid or myelomatous diseases.
•Group B) Subjects with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders

Exclusion Criteria

•Pregnant or lactating women.
•Subjects with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol.
•Subjects with uncontrolled, progressive infections.
•Subjects who are good candidates for long term disease control with standard chemotherapy or radiation or high dose therapy and autologous support.
•Subjects with active central nervous system (CNS) disease.
•Donor Inclusion Criteria:
•Donor must be capable of providing informed consent. If 14-17 years of age, a 'single patient exemption' from the local Institutional Review Board must be obtained.
•Donor must not have any medical condition which would make mobilization or apheresis more than a minimal risk, and should have the following:
•Adequate cardiac function by history and physical examination. Those with a history of cardiac failure or infarction should be evaluated by a cardiologist prior to donation
•Adequate hematopoietic function with hematocrit ≥ 30%, white blood cell count of 3000, and platelets 100,

Arms & Interventions

Cohort A - Lymphoid Disease

Group A: Patients with a high chance of progressive lymphoid or myelomatous disease undergo Non-myeloablative Stem Cell Transplantation.

Intervention: Non-myeloablative Stem Cell Transplantation

Cohort B - Myeloid Disease

Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders undergo Non-myeloablative Stem Cell Transplantation.

Intervention: Non-myeloablative Stem Cell Transplantation

Outcomes

Primary Outcomes

Disease Free Survival

Time Frame: 2 years

Estimate disease free survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. DFS was defined as the period of time between the day of transplantation and either disease relapse or death due to the disease. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants who were disease free at 2 years is reported by donor type.