Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Blastic Phase Chronic Myelogenous Leukemia, Childhood Burkitt Lymphoma, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, Childhood Myelodysplastic Syndromes, Childhood Nasal Type Extranodal NK/T-cell Lymphoma, Chronic Phase Chronic Myelogenous Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Anaplastic Large Cell Lymphoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent/Refractory Childhood Hodgkin Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Relapsing Chronic Myelogenous Leukemia, Secondary Myelodysplastic Syndromes, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Waldenström Macroglobulinemia
Conditions
Brief summary
This pilot phase II trial studies how well giving donor T cells after donor stem cell transplant works in treating patients with hematologic malignancies. In a donor stem cell transplant, the donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.
Detailed description
PRIMARY OBJECTIVES: I. To determine the feasibility of escalating dose regimen (EDR) donor lymphocyte infusion (DLI) as measured by the proportion of patients who receive at least one DLI. SECONDARY OBJECTIVES: I. To assess progression free survival (PFS) at 2 years after stem cell transplant (SCT) for high-risk hematologic malignancies receiving T-cell depleted grafts followed by escalating dose regimen (EDR) prophylactic DLI compared to historical controls not receiving DLI. II. To assess the safety of EDR DLI for high-risk hematologic malignancies as measured by cumulative incidence of severe grade III-IV acute graft-versus-host disease (GVHD). III. To measure outcomes of grade II-IV acute GVHD, non-relapse mortality, overall survival and chronic GVHD of EDR DLI. IV. To assess the full donor chimerism rate in the CD3 compartment and immune reconstitution after EDR DLI. OUTLINE: Patients receive DLI intravenously (IV). Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 2 years.
Interventions
Given IV
Correlative studies
Sponsors
Study design
Eligibility
Inclusion criteria
* INCLUSION CRITERIA PRIOR TO TRANSPLANT: * The clinical trial will be offered to all high risk (defined 3 below) patients with hematologic malignancies who require stem cell transplants as part of their standard of care using matched related or unrelated donors * Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following American Society for Blood and Marrow Transplantation (ASBMT) criteria, including but not limited to conditions listed; these criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning: * Refractory acute myelogenous or lymphoid leukemia * Relapsed acute myelogenous or lymphoid leukemia * Myelodysplastic syndromes with 5% or more blasts * Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase * Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant * High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen * DONORS: Matched related or unrelated donor stem cell transplant (SCT) matched at human leukocyte antigen (HLA) A- B, C, and DRB1 by molecular methods; 7 of 8 matched donor acceptable for related donors * T-cell depletion with anti-thymocyte globulin (ATG) (rabbit or horse) or at least 30 mg of alemtuzumab total in the conditioning regimen * Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant * Zubrod performance status (PS) 0-2 or equivalent Karnofsky PS * Eligible for allogeneic transplant in the treating physicians' judgment and by institutional standards * ELIGIBILITY TO RECEIVE DLI POST-TRANSPLANT: * Donor lymphocytes available or able to be collected * No evidence of disease by standard morphology; minimal residual disease or molecular evidence of disease will not exclude * Absolute neutrophil count \>= 500/μl * Platelet count \>= 20,000/μl without transfusion for 7 days * Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 5 x upper limit of normal (ULN) * Bilirubin =\< 3 x ULN * No evidence of grade II or higher acute GVHD or chronic GVHD at initiation of first DLI * No systemic corticosteroids or immunosuppressive drugs (topical acceptable); replacement steroids for adrenal insufficiency are not excluded
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Patients Who Are Able to Receive at Least One DLI Treatment | Up to 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 2 years | Time to relapse or death as a result of any cause was evaluated at 2 years and the progression free survival rate was reported. |
| Overall Survival (OS) | At 2 years | Computed using the Kaplan-Meier product-limit estimate and expressed as probabilities with a 95% CI. |
| Rate of Acute GVHD (aGVHD) With Any Grade | At 1 year and 2 year | Estimated by cumulative incidence method. |
| Rate of Chronic GVHD (cGVHD) | At 1 year and 2 year | Estimated by cumulative incidence method. |
| Treatment-related Mortality | At 2 year | Estimated by cumulative incidence method. Cumulative incidence of treatment-related mortality with relapse of the original disease as the competing risk will be calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (DLI) Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
therapeutic allogeneic lymphocytes: Given IV
laboratory biomarker analysis: Correlative studies | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 9 |
| Overall Study | Graft Failure | 1 |
| Overall Study | GVHD | 2 |
| Overall Study | Physician Decision | 17 |
| Overall Study | Relapse | 12 |
Baseline characteristics
| Characteristic | Treatment (DLI) |
|---|---|
| Age, Continuous | 53 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 70 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 36 |
| other Total, other adverse events | 1 / 36 |
| serious Total, serious adverse events | 12 / 36 |
Outcome results
Percentage of Patients Who Are Able to Receive at Least One DLI Treatment
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (DLI) | Percentage of Patients Who Are Able to Receive at Least One DLI Treatment | 36 Participants |
Overall Survival (OS)
Computed using the Kaplan-Meier product-limit estimate and expressed as probabilities with a 95% CI.
Time frame: At 2 years
Population: Patients received at least one DLI Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Overall Survival (OS) | 59.7 percentage of patients |
Progression Free Survival (PFS)
Time to relapse or death as a result of any cause was evaluated at 2 years and the progression free survival rate was reported.
Time frame: 2 years
Population: Patients received at least one DLI Treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Progression Free Survival (PFS) | 43 percentage of patients |
Rate of Acute GVHD (aGVHD) With Any Grade
Estimated by cumulative incidence method.
Time frame: At 1 year and 2 year
Population: Patients received at least one DLI Treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (DLI) | Rate of Acute GVHD (aGVHD) With Any Grade | At 1 year | 41.8 percentage of patients |
| Treatment (DLI) | Rate of Acute GVHD (aGVHD) With Any Grade | At 2 year | 41.8 percentage of patients |
Rate of Chronic GVHD (cGVHD)
Estimated by cumulative incidence method.
Time frame: At 1 year and 2 year
Population: Patients received at least one DLI treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (DLI) | Rate of Chronic GVHD (cGVHD) | At 1 year | 26.6 percentage of patients |
| Treatment (DLI) | Rate of Chronic GVHD (cGVHD) | At 2 year | 26.6 percentage of patients |
Treatment-related Mortality
Estimated by cumulative incidence method. Cumulative incidence of treatment-related mortality with relapse of the original disease as the competing risk will be calculated.
Time frame: At 2 year
Population: Patients received at least one DLI treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (DLI) | Treatment-related Mortality | 12.1 percentage of patients |