Enhancing Graft vs Leukemia Via Delayed Ex-Vivo Co-Stimulated DLI After Non-Myeloablative Stem Cell Transplantation

Sponsor

Abramson Cancer Center of the University of Pennsylvania (Other)

Overall Status

Completed

CT.gov ID

NCT00374933

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a new platform in non-myeloablative allogeneic stem cell transplantation to improve survival by harnessing the immunologic potential of donor T-cells to induce and maintain long-term remissions in patients with hematologic malignancies without undue toxicity. This study involves is the first study in humans directed at optimizing the graft vs leukemia effect by infusing activated T-cells from healthy donors prophylactically, months after recovery from the initial transplant. Investigators are studying whether the activation of donor cells prior to infusion will enhance the patient's ability to "seek and destroy" residual malignant cells while also helping the immune system to fight infection without increasing the immune reaction against the host.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndrome	Drug: Non-myeloablative allogeneic stem cell transplant with prophylactic activated DLI Drug: "Prophylactic" delayed ADLI Drug: "Prophylactic" delayed activated donor lymphocyte infusion	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Non-Myeloablative Conditioning With Allogeneic Peripheral Blood Progenitor Cell Transplantation Followed by Prophylactic Activated Donor Lymphocyte Infusion (DLI) for the Treatment of High Risk Acute Leukemia/MDS

Study Start Date :

Apr 1, 2007

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 "Prophylactic" delayed activated donor lymphocyte infusion (ADLI) after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation	Drug: Non-myeloablative allogeneic stem cell transplant with prophylactic activated DLI "Prophylactic" delayed activated donor lymphocyte infusion (ADLI) after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation Drug: "Prophylactic" delayed ADLI "Prophylactic" ADLI after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation Drug: "Prophylactic" delayed activated donor lymphocyte infusion "Prophylactic" delayed activated donor lymphocyte infusion (ADLI) after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation

Arm

Intervention/Treatment

Experimental: 1

"Prophylactic" delayed activated donor lymphocyte infusion (ADLI) after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation

Drug: Non-myeloablative allogeneic stem cell transplant with prophylactic activated DLI

"Prophylactic" delayed activated donor lymphocyte infusion (ADLI) after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation

Drug: "Prophylactic" delayed ADLI

"Prophylactic" ADLI after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation

Drug: "Prophylactic" delayed activated donor lymphocyte infusion

"Prophylactic" delayed activated donor lymphocyte infusion (ADLI) after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation

Outcome Measures

Primary Outcome Measures

Evaluate the safety and feasibility of administering prophylactic donor lymphocyte infusion (DLI) after non-myeloablative transplant (NMT). [Six months after last patient entered on study.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Patient-related Parameters:

Patients must have a healthy histocompatible donor (A, B and DR match); either sibling or unrelated volunteer identified through the NMDP
Age between 18 and 70 years old
Life expectancy greater than 3 months.
ECOG performance status 0-1.
Patients must have acceptable organ function:
total bilirubin <2.0
AST and ALT < 3 x normal, unless increases are thought to be either from non-hepatic causes (i.e hemolysis) or related to underlying disease (such as liver involvement with leukemia);
creatinine <2.0 or creatinine clearance >40 ml/min (calculated or collected);
Cardiac: An ejection fraction >40% on MUGA or echocardiogram;
Pulmonary: corrected DLCO >50%

Exclusion Criteria:

Subjects:

Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study. Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.
Patients with uncontrolled or untreated central nervous system involvement
Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
HIV positive patients are excluded
Pregnant women
Patients who are breastfeeding

Donors:

Sibling donors will be evaluated according to the standard practice of the University of Pennsylvania Bone Marrow and Stem Cell Transplant Program
Unrelated donor evaluations and consent will be performed by an NMDP donor center according to standard guidelines and procedures.