Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Evaluate the safety of natural killer (NK) cell infusion using CD56 monoclonal antibody selected with Miltenyi Biotec system following nonmyeloablative stem cell transplantation (SCT) from mismatched donors. This pilot study will evaluate toxicity including mortality, occurrence of acute graft versus host disease (aGVHD) and other severe toxicity.
The use of non-selected donor lymphocyte infusions (DLIs) (to help early immune recovery and induce antitumor response) following nonmyeloablative allogeneic stem cell transplantation (ASCT) is also complicated by the risk of acute graft versus host disease (aGVHD) with 30-40% of patients experiencing grade III-IV aGVHD. Data suggests that the use of natural killer (NK) cells (instead of nonselected DLIs) in this setting may mediate a graft versus tumor (GVT) effect independently of aGVHD.
This pilot study is designed to evaluate the efficacy and toxicity of donor natural killer (NK) cell selection and infusion following nonmyeloablative allogeneic stem cell transplantation from mismatched donors.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NK-CD56 | Experimental | NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NK-CD56 | Device | NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II aGVHD at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity | Evaluate the safety of NK cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplantation from mismatched donors: Toxicity including mortality, occurrence of acute graft versus host disease (aGVHD) and other severe toxicity. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy - Overall Survival | Evaluate the efficacy of the regimen in terms of overall survival (OS). | 7 years |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| David Rizzieri, MD | Duke University Health Systems | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Health Systems | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20188202 | Result | Rizzieri DA, Storms R, Chen DF, Long G, Yang Y, Nikcevich DA, Gasparetto C, Horwitz M, Chute J, Sullivan K, Hennig T, Misra D, Apple C, Baker M, Morris A, Green PG, Hasselblad V, Chao NJ. Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2010 Aug;16(8):1107-14. doi: 10.1016/j.bbmt.2010.02.018. Epub 2010 Feb 24. |
Not provided
Not provided
Prior to donor lymphocyte infusion (DLI), disease state was documented:
Complete history Physical exam Performance status Routine lab tests Radiographic tests Subjects didn't continue with treatment with disease progression. 2 subjects withdrew consent; 1 had graft versus host disease; 1 died; 1 subject's donor didn't yield enough cells.
21 Patients were recruited through the Adult Bone Marrow Transplant Program at Duke University Medical Center. Recruitment began in April, 2005 and ended in March, 2011. Patients who met the eligibility criteria were approached about the study and informed consent was conducted for those who agreed.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Experimental: NK-CD56 | NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors NK Cell Infusion following SCT from mismatched donors : The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II aGVHD at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who were eligible for study.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Experimental: NK-CD56 | Natural Killer (NK) Cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplant (SCT) from mismatched donors NK Cell Infusion following SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II acute graft-versus host disease (aGVHD) at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Toxicity | Evaluate the safety of NK cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplantation from mismatched donors: Toxicity including mortality, occurrence of acute graft versus host disease (aGVHD) and other severe toxicity. | Participants who were able to receive infusion. | Posted | Number | participants | 8 weeks |
|
Patients shall be monitored for toxicity and Graft versus Host Disease every other week until 8 weeks after the last Natural Killer cell Infusion and after that, every 4 weeks for 12 more weeks.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental: NK-CD56 | Natural Killer (NK) Cell infusion using CD56 monoclonal antibody following nonmyeloablative stem cell transplant (SCT) from mismatched donors NK Cell Infusion following SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II acute graft-versus host disease (aGVHD) at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Failure to Engraft | Investigations | CTCAE (3.0) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Rizzieri, MD | Duke University Medical Center | 919-668-1040 | david.rizzieri@duke.edu |
Not provided
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Efficacy - Overall Survival | Evaluate the efficacy of the regimen in terms of overall survival (OS). | Participants who completed infusion. | Posted | Mean | Full Range | months | 7 years |
|
|
|
| 0 |
| 16 |
| 16 |
| 16 |
| Atrial Fibrillation | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment | Supraventricular and nodal arrhythmia |
|
| Atrial Flutter | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment | Supraventricular and nodal arrhythmia |
|
| Dermatology - Skin (other) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment | Squamous cell carcinoma - left chest |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment | desquamation - contact dermatitis on neck and face |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Esophagitis | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment | ulcerative esophagitis |
|
| Hemorrhagic Cystitis | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Hemorrhage - GU | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Febrile Neutropenia | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | fever of unknown origin without clinically or microbiologically documented infection)(ANC <1.0 x 10e9/L, fever >=38.5 degrees C |
|
| Infection - other | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Cytomegalovirus Retinitis |
|
| Infection-bacterial with grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | C-diff; Gram-rod bacteria; Methicillin-resistant Staphylococcus aureus (MRSA); Klebsiella; E-coli; Bacillus and Coag Negative Staph |
|
| Infection-bacterial with normal ANC or grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Osteomyelitis; Pseudomonas bacteremia; Staph; Enterococcus |
|
| Infection-viral without febrile neutropenia | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Cytomegalovirus; Viremia; Parainfluenza |
|
| Hyperbilirubinemia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| AST; SGOT | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment | Aspartate transaminase; serum glutamic oxaloacetic transaminase |
|
| Creatinine | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment | 4.3 mg/dl |
|
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Neuropathy | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment | Motor neuropathy |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Secondary Malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (3.0) | Non-systematic Assessment | Post-transplant lymphoproliferative disorder |
|
| Erectile Dysfunction | Reproductive system and breast disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Blood/Bone Marrow - Blast Crisis | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment | Relapsed Acute myeloid leukemia |
|
| Infection-viral with normal ANC or grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Cytomegalovirus; Viremia; Polyoma; Herpes; Varicella Zoster |
|
| Infection-viral with Grade 3 or 4 neutrophils (ANC <1.0 x 10e | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Adenovirus; Cytomegalovirus; Parainfluenza; Polyoma; Human Herpes Virus 6; Viremia |
|
| Hypervolemia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Infection-bacterial without febrile neutropenia | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Gram positive Cocci bacteria |
|
Not provided
Not provided
Not provided
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |