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

Primary Purpose

Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Therapeutic Allogeneic Lymphocytes
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • VA Puget Sound Health Care System
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • Universitaet Leipzig
  • University of Torino

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (DLI)

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD
Percentage of Participants with Grade IV Acute GVHD

Secondary Outcome Measures

Incidence of Graft Rejection
Percentage patients with graft rejection.
Incidence of Relapse/Progression
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever >38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%. CMML, AML, ALL >30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL ≥1 of: Physical exam/imaging studies ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
Incidence of Grade II-IV GVHD in Patients Undergoing DLI Following a Non-myeloablative Transplant
Percentage of Participants with II-IV Acute GVHD
Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant
Percentage of Participants with infections.
Overall Survival
Percentage patients surviving 1 year post-transplant.
Progression-free Survival
Percentage of patients with progression-free survival

Full Information

First Posted
September 10, 2003
Last Updated
January 15, 2020
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00068718
Brief Title
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

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
May 2003 (Actual)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (DLI)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Therapeutic Allogeneic Lymphocytes
Other Intervention Name(s)
Allogeneic Lymphocytes
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD
Description
Percentage of Participants with Grade IV Acute GVHD
Time Frame
100 days after DLI
Secondary Outcome Measure Information:
Title
Incidence of Graft Rejection
Description
Percentage patients with graft rejection.
Time Frame
100 days after DLI
Title
Incidence of Relapse/Progression
Description
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever >38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%. CMML, AML, ALL >30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL ≥1 of: Physical exam/imaging studies ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
Time Frame
1 year after DLI
Title
Incidence of Grade II-IV GVHD in Patients Undergoing DLI Following a Non-myeloablative Transplant
Description
Percentage of Participants with II-IV Acute GVHD
Time Frame
100 days after DLI
Title
Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant
Description
Percentage of Participants with infections.
Time Frame
100 days after DLI
Title
Overall Survival
Description
Percentage patients surviving 1 year post-transplant.
Time Frame
1 year after DLI
Title
Progression-free Survival
Description
Percentage of patients with progression-free survival
Time Frame
1 year after DLI

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brenda Sandmaier
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Puget Sound Health Care System
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Universitaet Leipzig
City
Leipzig
ZIP/Postal Code
D-04103
Country
Germany
Facility Name
University of Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

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

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