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
Conditions
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.
Interventions
BIOLOGICALTherapeutic Allogeneic Lymphocytes
Given IV
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD | 100 days after DLI | Percentage of Participants with Grade IV Acute GVHD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Relapse/Progression | 1 year after DLI | 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 | 100 days after DLI | Percentage of Participants with II-IV Acute GVHD |
| Incidence of Graft Rejection | 100 days after DLI | Percentage patients with graft rejection. |
| Overall Survival | 1 year after DLI | Percentage patients surviving 1 year post-transplant. |
| Progression-free Survival | 1 year after DLI | Percentage of patients with progression-free survival |
| Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant | 100 days after DLI | Percentage of Participants with infections. |
Countries
Germany, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Therapeutic Allogeneic Lymphocytes: Given IV | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Treatment (DLI) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 59.2 years |
| Region of Enrollment Italy | 9 participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 35 |
| serious Total, serious adverse events | 6 / 35 |
Outcome results
Primary
Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD
Percentage of Participants with Grade IV Acute GVHD
Time frame: 100 days after DLI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD | 5.7 percentage of participants |
Secondary
Incidence of Grade II-IV GVHD in Patients Undergoing DLI Following a Non-myeloablative Transplant
Percentage of Participants with II-IV Acute GVHD
Time frame: 100 days after DLI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Incidence of Grade II-IV GVHD in Patients Undergoing DLI Following a Non-myeloablative Transplant | 14.3 percentage of participants |
Secondary
Incidence of Graft Rejection
Percentage patients with graft rejection.
Time frame: 100 days after DLI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Incidence of Graft Rejection | 5.7 percentage of participants |
Secondary
Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant
Percentage of Participants with infections.
Time frame: 100 days after DLI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant | 88.6 percentage of participants |
Secondary
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.
Time frame: 1 year after DLI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Incidence of Relapse/Progression | 71.4 percentage of participants |
Secondary
Overall Survival
Percentage patients surviving 1 year post-transplant.
Time frame: 1 year after DLI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Overall Survival | 71.4 percentage of participants |
Secondary
Progression-free Survival
Percentage of patients with progression-free survival
Time frame: 1 year after DLI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Progression-free Survival | 28.6 percentage of participants |