Clinical trial NCT00068718: Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant
Official title: Donor Lymphocyte Infusion for the Treatment of Malignancy After Hematopoietic Cell Transplantation Using Nonmyeloablative Conditioning - A Multi-center Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Hodgkin Lymphoma
Recurrent Non-Hodgkin Lymphoma
Recurrent Plasma Cell Myeloma
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-11
Enrollment: 35
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I/II trial studies the side effects of donor lymphocyte infusion and to see how well it works in treating patients with persistent, relapsed (disease that has returned), or progressing cancer after donor hematopoietic cell transplantation. White blood cells from donors may be able to kill cancer cells in patients with cancer that has come back (recurrent) after a donor hematopoietic cell transplant.

Detailed description: PRIMARY OBJECTIVES:

I. To assess the safety of donor lymphocyte infusion (DLI) as adoptive immunotherapy for persistent or relapsed malignant diseases in patients after related or unrelated nonmyeloablative transplantation.

SECONDARY OBJECTIVES:

I. To determine disease response, progression free and overall survival, chimerism, grade of graft-versus-host disease (GVHD), and infections.

OUTLINE:

Patients undergo unirradiated DLI over 15-30 minutes on day 0. Patients then undergo restaging on day 28 and may undergo a second DLI after at least 4 weeks if no significant GVHD develops and disease status worsens or after at least 8 weeks if disease status is unchanged and persistent donor T-cells are documented.

After completion of study treatment, patients are followed up periodically.

Eligibility criteria: Inclusion Criteria:

* Only patients having received a preceding nonmyeloablative allogeneic transplantation with fludarabine/2 Gy total-body irradiation (TBI) - 4 Gy TBI or 2 Gy TBI - 4 Gy TBI conditioning from either a related or unrelated donor are eligible for this protocol
* Patients with persistent, relapsed or progressing malignancy after nonmyeloablative allogeneic transplantation; persistent disease will be defined as a failure to achieve a response as compared to baseline
* Patients with rapidly progressing malignancies (acute myeloid leukemia \[AML\], acute lymphocytic leukemia \[ALL\], blastic phase chronic myelogenous leukemia \[CML-BC\] intermediate-high-grade non-Hodgkin lymphoma \[NHL\], Hodgkin's lymphoma or aggressive multiple myeloma \[MM\]) should receive salvage chemotherapy or radiation before DLI according to the recommendation made in this protocol; any form of salvage chemotherapy should be discontinued no less than 3 weeks before DLI; therapy with Gleevec or interferon (IFN)-alpha should be discontinued prior to DLI; after salvage chemotherapy restaging is performed, patients with progressive disease and patients not meeting the inclusion criteria of the study after chemotherapy will be excluded from the study; patients are allowed to receive further doses of chemotherapy after DLI administration if they are scheduled for further DLI; after additional therapy the patients must be restaged and must again meet inclusion criteria to receive further DLI
* Patients must be able to tolerate a taper of systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day; all other immunosuppressive therapy must have been discontinued for at least two weeks without significant flares in GVHD (i.e., increase of acute GVHD by one or more grades)
* Patients must have persistent donor cluster of differentiation (CD)3 cells (\> 5% donor CD3 cells by a deoxyribonucleic acid \[DNA\]-based assay that compares the profile of amplified fragment length polymorphisms \[ampFLP\] \[or fluorescent in situ hybridization (FISH) studies or variable number tandem repeat (VNTR)\])
* DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected cryopreserved peripheral blood stem cells (PBSC) after mobilization with granulocyte colony-stimulating factor (G-CSF) or cryopreserved unmodified leukapheresis product from the original donor can be used; if cryopreserved product is not available, the DLI product must be from the original donor of hematopoietic cell transplantation
* DONOR: Original donor of hematopoietic cell transplantation
* DONOR: Donor must give consent to leukapheresis
* DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian)
* DONOR: Donor must be medically fit to undergo the apheresis procedure (institutional guidelines for apheresis)

Exclusion Criteria:

* Current grade II to IV acute GVHD or extensive chronic GVHD
* Karnofsky score \< 50%
* Lansky Play-Performance Score \< 40 for pediatric patients
* DONOR: Donors who are not suitable for medical reasons to donate peripheral blood mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the American Association of Blood Banks (AABB)
* DONOR: Pregnancy
* DONOR: Human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection
* DONOR: Recent immunization may require a delay

Primary outcomes:
measure: Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD
timeFrame: 100 days after DLI
Secondary outcomes:
measure: Incidence of Graft Rejection
timeFrame: 100 days after DLI
measure: Incidence of Relapse/Progression
timeFrame: 1 year after DLI
measure: Incidence of Grade II-IV GVHD in Patients Undergoing DLI Following a Non-myeloablative Transplant
timeFrame: 100 days after DLI
measure: Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant
timeFrame: 100 days after DLI
measure: Overall Survival
timeFrame: 1 year after DLI
measure: Progression-free Survival
timeFrame: 1 year after DLI
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
city: Leipzig
country: Germany
facility: Universitaet Leipzig
city: Torino
country: Italy
facility: University of Torino
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Brenda Sandmaier
role: PRINCIPAL_INVESTIGATOR
References: