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
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 18
Study Start Date: April 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00374933

Locations
United States, Pennsylvania
Abramson Cancer Center at University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Steven Goldstein, M.D. University of Pennsylvania
  More Information

No publications provided

Responsible Party: Carl June, MD, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00374933     History of Changes
Other Study ID Numbers: UPCC 08405
Study First Received: September 11, 2006
Last Updated: September 29, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
AML
ALL
MDS
Allogeneic transplant
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Adoptive cell therapy
Non-myeloablative

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on April 15, 2014