Clinical trial NCT00374933: Enhancing Graft vs Leukemia Via Delayed Ex-Vivo Co-Stimulated DLI After Non-Myeloablative Stem Cell Transplantation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Keywords: AML
ALL
MDS
Allogeneic transplant
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Adoptive cell therapy
Non-myeloablative
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2006-09-12
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the safety and feasibility of administering prophylactic donor lymphocyte infusion (DLI) after non-myeloablative transplant (NMT).
timeFrame: Six months after last patient entered on study.
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center at University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Steven Goldstein, M.D.
role: PRINCIPAL_INVESTIGATOR
References: