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

NCT00674427 | Terminated Phase 1 FDA Drug

• 1 other identifier: 805534 UPCC 20406
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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).

Conditions

Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Hodgkin's Disease; Multiple Myeloma; Chronic Lymphocytic Leukemia

Keywords

AML; ALL; MDS; CLL; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Determining the incidence and severity of acute and chronic GVHD associated with repetitive dosing of aDLI.

  3 years

Study Arms (2)

CR

EXPERIMENTAL

Subjects who are in CR ater 6-12 weeks after aDLI

Biological: CD3/CD28 Activated T cells

Not in CR

EXPERIMENTAL

Subjects not in CR after 6-12 weeks after aDLI

Biological: CD3/CD28 Activated T cells

Interventions

CD3/CD28 Activated T cells BIOLOGICAL

Subjects who are not in CR will receive one infusion of high dose aDLI

Not in CR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, B-Cell

Study Officials

• David Porter, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: May 7, 2008
• Study Start: January 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: August 17, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)