Lymphoid Leukemia, Acute, Myeloid Malignancy, Plasma Cell Tumor
Conditions
Brief summary
This pilot study is being conducted to treat patients who have a certain type of malignancy (lymphoid or myeloid) with immune effector cells after a T-cell depleted allogeneic hematopoietic cell transplantation (TCD HSCT). This study is designed to see whether an investigational cellular product of immune cells obtained from a donor's cells that have been treated so that the type of cells that can lead to graft vs host disease have been removed can be safely administered. These cell products are administered following the initial stem cell transplant to assess the effect and improvement on minimal residual disease status, infectious complication, progression-free and overall survival.
Interventions
BIOLOGICALT-cell Receptor α/β Depleted Donor Lymphocyte Infusions
T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients
Sponsors
Guenther Koehne
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The model is both parallel and sequential, in that Matched and Mismatched strata run in parallel and independently. Within each stratum, Cohorts I-III are filled sequentially. In addition, Cohort I of each stratum has three groups (A-C) that are filled sequentially.
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Patients with hematologic malignancies that are candidates CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation. * Patients must have a Karnofsky (adult) Performance Status of at least 70%. * Patients must have adequate organ function measured by: * Cardiac: asymptomatic or if symptomatic then left ventricular ejection fraction (LVEF) at rest must be 50% and must improve with exercise. * Hepatic: \< 3x upper limit of normal (ULN) AST and \< 1.5 mg/dL total serum bilirubin, unless there is congenital benign hyperbilirubinemia. Patients with higher bilirubin levels due to causes other than active liver disease is also eligible with Pl approval (e.g., patients with PNH, Gilbert's disease or other hemolytic disorders). * Renal: serum creatinine: ≤ 1.2 mg/dL or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) \> 40 mL/min (measured or calculated/estimated). * Pulmonary: asymptomatic or if symptomatic, diffusing capacity of the lungs for carbon monoxide (DLCO) 50% of predicted (corrected for hemoglobin). * Each patient must be willing to participate as a research subject and must sign an informed consent form.
Exclusion criteria
* Patients with active acute GvHD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs) | 30 days post-infusion | TE-SAEs are defined as the composite of death, non-fatal pulmonary embolism, stroke, acute graft versus host disease (GvHD), and clinically significant laboratory test abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Remission | 2 years | Remission - measured by absence of signs and symptoms |
| Number of Participants With Transplant-associated Viral Complications | 2 years | Transplant-associated viral complications - measured by viral infections associated with transplant |
| Disease Free Survival- Measured by Absence of Relapse/Recurrence or Death. | 2 years | Disease free survival - measured by (absence of ) relapse/recurrence or death. Relapse and recurrence, both will be measured by greater than 5% circulating leukemic blasts in the marrow or peripheral blood and/or the presence of blasts in any extra medullary site and/or disease determined by clinical assessment. |
| Overall Survival | 2 years | Overall survival - measured by death |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HLA Matched Cohort I 5 x 10\^5/kg at 6-7 weeks post-transplant (Group A), 4-5 weeks post-transplant (Group B), or 2-3 weeks post-transplant (Group C)
T-cell Receptor α/β Depleted Donor Lymphocyte Infusions: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients | 10 |
| HLA Matched Cohort II 5 x 10\^5/kg starting time point X (whichever was safest as determined by Matched Cohort I), 1 x 10\^6/kg 3-4 weeks after first dose, and 1 x 10\^6/kg 3-4 weeks after second dose
T-cell Receptor α/β Depleted Donor Lymphocyte Infusions: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients | 0 |
| HLA Matched Cohort III 5 x 10\^5/kg starting time point X (whichever was safest as determined by Matched Cohort I), 1 x 10\^6/kg 3-4 weeks after first dose, and 2 x 10\^6/kg 3-4 weeks after second dose
T-cell Receptor α/β Depleted Donor Lymphocyte Infusions: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients | 0 |
| HLA Mismatched Cohort I 1 x 10\^5/kg at 6-7 weeks post-transplant (Group A), 4-5 weeks post-transplant (Group B), or 2-3 weeks post-transplant (Group C)
T-cell Receptor α/β Depleted Donor Lymphocyte Infusions: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients | 1 |
| HLA Mismatched Cohort II 1 x 10\^5/kg starting time point Y (whichever was safest as determined by Mismatched Cohort I), 5 x 10\^5/kg 3-4 weeks after first dose, and 5 x 10\^5/kg 3-4 weeks after second dose
T-cell Receptor α/β Depleted Donor Lymphocyte Infusions: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients | 0 |
| HLA Mismatched Cohort III 1 x 10\^5/kg starting time point Y (whichever was safest as determined by Mismatched Cohort I), 5 x 10\^5/kg 3-4 weeks after first dose, and 1 x 10\^6/kg 3-4 weeks after second dose
T-cell Receptor α/β Depleted Donor Lymphocyte Infusions: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients | 0 |
| Total | 11 |
Baseline characteristics
| Characteristic | Total | HLA Matched Cohort II | HLA Matched Cohort III | HLA Mismatched Cohort I | HLA Mismatched Cohort II | HLA Mismatched Cohort III | HLA Matched Cohort I |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
| Age, Continuous | 60.1 years STANDARD_DEVIATION 13.6 | — | — | 57 years STANDARD_DEVIATION 0 | — | — | 60.4 years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | — | — | 0 Participants | — | — | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | — | — | 1 Participants | — | — | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | — | — | 0 Participants | — | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | — | — | 0 Participants | — | — | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | — | — | 1 Participants | — | — | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | — | — | 0 Participants | — | — | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | — | — | 0 Participants | — | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | — | — | 0 Participants | — | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | — | — | 0 Participants | — | — | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | — | — | 0 Participants | — | — | 10 Participants |
| Region of Enrollment United States | 11 participants | — | — | 1 participants | — | — | 10 participants |
| Sex: Female, Male Female | 4 Participants | — | — | 0 Participants | — | — | 4 Participants |
| Sex: Female, Male Male | 7 Participants | — | — | 1 Participants | — | — | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 10 | 0 / 0 | 0 / 0 | 1 / 1 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 10 / 10 | 0 / 0 | 0 / 0 | 1 / 1 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 6 / 10 | 0 / 0 | 0 / 0 | 1 / 1 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs)
TE-SAEs are defined as the composite of death, non-fatal pulmonary embolism, stroke, acute graft versus host disease (GvHD), and clinically significant laboratory test abnormalities.
Time frame: 30 days post-infusion
Population: The study was terminated so we did not yet accrue to some cohorts, as the cohorts were filled sequentially.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HLA Matched Cohort I | Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs) | 1 Participants |
| HLA Matched Cohort II | Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs) | 0 Participants |
| HLA Matched Cohort III | Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs) | 0 Participants |
| HLA Mismatched Cohort I | Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs) | 0 Participants |
| HLA Mismatched Cohort II | Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs) | 0 Participants |
| HLA Mismatched Cohort III | Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs) | 0 Participants |
Secondary
Disease Free Survival- Measured by Absence of Relapse/Recurrence or Death.
Disease free survival - measured by (absence of ) relapse/recurrence or death. Relapse and recurrence, both will be measured by greater than 5% circulating leukemic blasts in the marrow or peripheral blood and/or the presence of blasts in any extra medullary site and/or disease determined by clinical assessment.
Time frame: 2 years
Population: Because the study was terminated early, no participants completed 2 years.
Secondary
Number of Participants in Remission
Remission - measured by absence of signs and symptoms
Time frame: 2 years
Population: Because the study was terminated early, no participants completed 2 years.
Secondary
Number of Participants With Transplant-associated Viral Complications
Transplant-associated viral complications - measured by viral infections associated with transplant
Time frame: 2 years
Population: Because the study was terminated early, no participants completed 2 years
Secondary
Overall Survival
Overall survival - measured by death
Time frame: 2 years
Population: Because the study was terminated early, no participants completed 2 years.