Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial of Donor Lymphocyte Infusion (DLI) and Activated DLI Following Relapse After Allogeneic Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00674427
Recruitment Status : Terminated (Insufficient funds)
First Posted : May 7, 2008
Last Update Posted : August 17, 2020
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:

This study is for patients with relapsed of disease after allogeneic bone marrow

The donor's T cells are activated by exposure to 2 compounds or antibodies that bind (or stick to) two compounds on T cells called CD3 and CD28. When these antibodies stick to both CD3 and CD28 on the T cells, the T cells becomes stimulated (or "activated") and grows. CD3 and CD28 are the coating of a T cell and a T cell is part of the body's immune system.

It is believed that when T cells are exposed to both of antibodies to CD3 and CD28 compounds at the same time, they become activated or "stimulated" and may be more effective in fighting infections or cancer cells. We call this therapy "activated donor lymphocyte infusions, or activated DLI (aDLI)".

This current study is being performed to see whether it is safe and effective to administer higher doses of activated DLI or repeated doses of activated DLI.

All patients will receive standard donor lymphocyte infusions first, and in addition will receive activated donor lymphocytes approximately 12 days later (DLI followed by aDLI). Depending on the response to this treatment, and depending on possible side effects (such as graft-vs-host disease as described below), patients in remission will then receive additional aDLI every 3 months for 4 more times, and patients not in remission within 6-12 weeks will receive higher dose aDLI. The timing of the higher dose aDLI will be determined by your physician depending on your disease and the rate of progression of your disease. The aDLI can be given as early as 6 weeks, or as late as 12 weeks (3 months).


Condition or disease Intervention/treatment Phase
Chronic Myelogenous Leukemia Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndrome Non-Hodgkin's Lymphoma Hodgkin's Disease Multiple Myeloma Chronic Lymphocytic Leukemia Biological: CD3/CD28 Activated T cells Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial Of DLI And Activated DLI (ADLI) Followed By Either Repetitive Dosing Of ADLI Or Dose Escalated ADLI For Patients With Relapse After Allogeneic Stem Cell Transplantation
Study Start Date : January 2008
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012


Arm Intervention/treatment
Experimental: CR
Subjects who are in CR ater 6-12 weeks after aDLI
Biological: CD3/CD28 Activated T cells
Subjects in CR 6-12 weeks after the first dose of Activated Donor Lymphocyte Infusion (aDLI) will continue to receive aDLI every 3 months for up to a year.

Experimental: Not in CR
Subjects not in CR after 6-12 weeks after aDLI
Biological: CD3/CD28 Activated T cells
Subjects who are not in CR will receive one infusion of high dose aDLI




Primary Outcome Measures :
  1. Determining the incidence and severity of acute and chronic GVHD associated with repetitive dosing of aDLI. [ Time Frame: 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Prior allogeneic stem cell transplant.
  • Expected survival > 4 weeks
  • Original bone marrow donor available for leukocyte donation.
  • Absence of active acute GVHD > grade I, or chronic GVHD.
  • Off all immune suppression for GVHD for 28 days (an exception may be made for patients with acute leukemia whose disease is progressing rapidly and a 28 day waiting period after discontinuation of immune suppression is not practical or appropriate).
  • Creatinine < 2.5 mg/dl.
  • Relapsed or persistent advanced malignancy with less than a 50% chance of responding to unstimulated DLI:

    a. CML: Relapse with accelerated phase, or blast phase disease b. AML, ALL i. Cytogenetic relapse (less than 5% blasts).

    1. The patient's leukemia-specific chromosome abnormality is detectable by standard cytogenetics in more than 25% of cells at any time greater than day 50 post-transplant.

      ii. Hematologic relapse: More than 5% blasts in the marrow or peripheral blood.

      c. MDS d. Non-Hodgkin's Lymphoma or Hodgkin's Disease i. Relapse: Recurrent disease by serial physical exam, radiographic studies, or molecular studies. If possible, tumor should be re-biopsied to determine histology and rule out possibility of EBV-related lymphoproliferative disease e. CLL f. Myeloma

      Exclusion Criteria:

  • Active chronic or acute GVHD > grade I.
  • Requirement for active immunosuppression to treat GVHD.
  • Pregnant or lactating women. The safety of this therapy on unborn children or effects on breast milk are not known.
  • Uncontrolled active infection
  • Any uncontrolled active medical disorder that would preclude participation as outlined.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00674427


Locations
Layout table for location information
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Layout table for investigator information
Principal Investigator: David Porter, MD University of Pennsylvania
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00674427    
Other Study ID Numbers: 805534 UPCC 20406
First Posted: May 7, 2008    Key Record Dates
Last Update Posted: August 17, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Pennsylvania:
AML
ALL
MDS
CLL
Multiple Myeloma
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Multiple Myeloma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Hodgkin Disease
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Lymphoma
Lymphatic Diseases
Leukemia, Lymphoid
Leukemia, B-Cell
Myeloproliferative Disorders