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

This study has been completed.
Sponsor:
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00374933
First received: September 11, 2006
Last updated: September 29, 2010
Last verified: September 2010

September 11, 2006
September 29, 2010
April 2007
December 2009   (final data collection date for primary outcome measure)
Evaluate the safety and feasibility of administering prophylactic donor lymphocyte infusion (DLI) after non-myeloablative transplant (NMT). [ Time Frame: Six months after last patient entered on study. ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00374933 on ClinicalTrials.gov Archive Site
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Enhancing Graft vs Leukemia Via Delayed Ex-Vivo Co-Stimulated DLI After Non-Myeloablative Stem Cell Transplantation
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myelogenous Leukemia
  • Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndrome
  • 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
Experimental: 1
"Prophylactic" delayed activated donor lymphocyte infusion (ADLI) after non-myeloablative conditioning and allogeneic peripheral blood cell stem cell transplantation
Interventions:
  • Drug: Non-myeloablative allogeneic stem cell transplant with prophylactic activated DLI
  • Drug: "Prophylactic" delayed ADLI
  • Drug: "Prophylactic" delayed activated donor lymphocyte infusion
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
December 2009
December 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

Disease related Parameters The following categories of patients with High Risk Acute Myelogenous Leukemia, MDS, or Acute Lymphoblastic Leukemia in first or second complete remission, age less than 70 years old, who would be offered a traditional allogeneic stem cell transplant but are ineligible for, or unwilling to undergo, Allo SCT, will be eligible for this study.

High Risk AML in CR1 is defined as having one of the following:

  • Intermediate or Poor risk cytogenetics at presentation; Extramedullary involvement (other than CNS); High WBC at presentation (>20,000); AML evolving out of Myelodysplasia, regardless of cytogenetics M3 in CR2 only
  • Patients with residual myelodysplasia after induction chemotherapy for AML
  • Patients who require a second course of induction chemotherapy to achieve remission status are felt to be inherently at high risk and will be considered eligible for this study

MDS-Patients deemed to have high risk MDS based on IPSS of >1.5 are eligible for this study. Patients must have less than 5% blasts at time of study entry and may receive induction chemotherapy prior to transplant.

High Risk Acute Lymphoblastic Leukemia pts in CR1 3.1.4 CR2 (including AML,M3) patients: Patients with AML or ALL who have relapsed and have received salvage chemotherapy at the discretion of their primary physician and meet criteria for CR2 are eligible

Not a candidate for standard myeloablative conditioning with allotransplantation. Patients are typically ineligible for standard allo SCT because of age greater than 50, or because of co-morbid disease that precludes myeloablative conditioning (such as coronary artery disease or cardiomyopathy, poor pulmonary function, or other medical disorders that, in the opinion of the patients transplant physician, would result in unacceptable toxicity from standard myeloablative conditioning with allogeneic transplantation).

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 may not 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 may not have uncontrolled or untreated central nervous system involvement
  • Patients may not have 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
  • The effects of these chemotherapy agents are likely to be harmful to a developing human fetus. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Pregnant women are excluded from this study because the chemotherapy is potentially teratogenic or has abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, patients who are breastfeeding should discontinue breastfeeding or will be excluded from this trial
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, patients who are breastfeeding should discontinue breastfeeding or will be excluded from this trial

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.
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00374933
UPCC 08405
Not Provided
Carl June, MD, University of Pennsylvania
University of Pennsylvania
Not Provided
Principal Investigator: Steven Goldstein, M.D. University of Pennsylvania
University of Pennsylvania
September 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP