Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00068718
First received: September 10, 2003
Last updated: July 31, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
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
Biological: Therapeutic Allogeneic Lymphocytes
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Donor Lymphocyte Infusion for the Treatment of Malignancy After Hematopoietic Cell Transplantation Using Nonmyeloablative Conditioning - A Multi-center Trial

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Safety of DLI following a non-myeloablative transplant, defined as incidence of grade IV acute GVHD [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Following the Fred Hutchinson Cancer Research Center (FHCRC) guidelines for serious adverse event (SAE) reporting.


Secondary Outcome Measures:
  • Effect of DLI on chimerism following a non-myeloablative transplant [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Outside institutions may use VNTR analysis (sex- matched transplants) or sex chromosome FISH-analysis (sex-mismatched transplants).

  • Effect of DLI on disease response following a non-myeloablative transplant [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Response criteria are defined according to disease.

  • Incidence of grade II-IV GVHD in patients undergoing DLI following a non-myeloablative transplant [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Following the FHCRC guidelines for SAE reporting.

  • Incidence of infections in patients undergoing DLI following a non-myeloablative transplant [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Following the FHCRC guidelines for SAE reporting.

  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: May 2003
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (DLI)
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.
Biological: Therapeutic Allogeneic Lymphocytes
Given IV
Other Names:
  • Allogeneic Lymphocytes
  • Therapeutic Allogeneic Lymphocytes

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068718

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
VA Puget Sound Health Care System
Seattle, Washington, United States, 98101
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Italy
University of Torino
Torino, Italy, 10126
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Brenda Sandmaier Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00068718     History of Changes
Other Study ID Numbers: 1803.00, NCI-2010-00163, 1803.00, P01CA078902, P30CA015704
Study First Received: September 10, 2003
Last Updated: July 31, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Blast Crisis
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Blood Protein Disorders
Bone Marrow Diseases
Carcinogenesis
Cardiovascular Diseases
Cell Transformation, Neoplastic
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplastic Processes
Paraproteinemias
Pathologic Processes

ClinicalTrials.gov processed this record on August 27, 2015