A Phase 1/2 interventional study of Infusion of donor lymphocytes in Immunodeficiency, sponsored by Wake Forest University Health Sciences. Terminated at 1 site in United States. Open to participants aged Up to 30 Years. Per ClinicalTrials.gov, last updated 2022-04-22.
Sponsored by Wake Forest University Health Sciences · Phase 1/2, Interventional, and Treatment
The purpose of this study is to determine the ability of a donor lymphocyte infusion (DLI) given with methotrexate to hasten immune recovery without causing severe graft-versus-host disease (GVHD) in recipients who have had a T-cell depleted transplant.
Studies have shown that giving donor T cells after a mismatched T cell-depleted stem cell transplant can speed up recovery of T cells in the patient. This approach can cause severe graft versus host disease (GVHD). The purpose of this study is to determine whether giving a donor lymphocyte infusion (DLI) with methotrexate can accelerate immune recovery in recipients of T cell-depleted stem cell transplants. Thirty days after a T-cell depleted transplant, patients will be given a DLI. They will be monitored for immune recovery as measured by CD4 count and for GVHD toxicity.
Patients will be separated into six cohorts based on dose of DLI received: 3 x 10\^4, 4 x 10\^4, 5 x 10\^4, 6 X 10\^4, 8 x 10\^4, and 10 X10\^4 cells/ kg of body weight. A minimum of 3 patients will be tested at each dose starting with the lowest dose. Dose escalation will continue until the dose associated with CD4 count >100 at Day +120 after transplant without significant GVHD is determined. All patients will receive thirteen doses of methotrexate after the DLI to prevent GVHD. Patients will be followed for 2 years for outcomes.
698 studies on the registry are indexed under Immunologic Deficiency Syndromes; 67 are open to participants now.
This study's enrollment of 38 is below the median of 56 across 455 interventional studies indexed under Immunologic Deficiency Syndromes.
Browse Immunologic Deficiency Syndromes studies →Wake Forest University Health Sciences is the lead sponsor of 1,320 studies on the registry; 199 are open to participants now.
Of its 323 completed or terminated interventional studies of FDA-regulated products, 243 (75%) have results posted.
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Exclusion Criteria:
Patients will receive an infusion of donor lymphocyte after T-cell depleted transplant.
Biological: Infusion of donor lymphocytes
A donor lymphocyte infusion will be given to provide T cells. There will be a dose escalation: 3 x 10\^4, 4 x 10\^4, 5 x 10\^4, 6 X 10\^4, 8 x 10\^4, and 10 X10\^4 cells/kg body weight. At least three patients will be assessed at each dose to determine safety before dose is increased.
Number of Participants With Immune Recovery Following Transplantation
Immune recovery was measured by CD4+ cells \> 100/μL by Day 120 following transplantation
Time frame: 120 days after transplant
Incidence and Severity of GVHD
Patients were evaluated for acute GVHD due to prophylactic DLI between the day of prophylactic DLI infusion and Day +180 after transplant. GVHD was graded using standard criteria.
Time frame: 180 days after transplant
Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD)
Subjects were actively monitored for adenovirus, cytomegalovirus (CMV), human herpes virus 6 (HHV6), and Epstein-Barr virus (EBV) as part of standard post-transplant care. All infections were collected from date of DLI until 1 year after transplant.
Time frame: 1 year
Patients who received a CD34+ selected peripheral blood stem cell (PBSC) transplant on the companion study, LCH BMT 09-01, at Levine Children's Hospital between December 2009 and June 2016.
| Milestone | MMRD: 3 x 10^4/kg DLI + MTX to Day +24 | MMRD: 3 x 10^4/kg DLI + MTX to Day +52 | MMRD: 4 x 10^4/kg DLI + MTX to Day +52 | MMRD: 4 x 10^4/kg DLI + MTX to Day +80 | MMRD: 5 x 10^4/kg DLI + MTX to Day +80 | MUD: 3 x 10^4/kg DLI + MTX to Day +24 | MUD: 3 x 10^4/kg DLI + MTX to Day +52 |
|---|---|---|---|---|---|---|---|
| Started | 4 | 4 | 3 | 14 | 10 | 1 | 2 |
| Completed | 3 | 2 | 2 | 10 | 9 | 1 | 1 |
| Not completed | 1 | 2 | 1 | 4 | 1 | 0 | 1 |
| Withdrew: Received subsequent therapy | 1 | 2 | 0 | 4 | 1 | 0 | 1 |
| Withdrew: Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Immune recovery was measured by CD4+ cells \> 100/μL by Day 120 following transplantation
| Participants | MMRD: 3 x 10^4/kg DLI + MTX to Day +24 | MMRD: 3 x 10^4/kg DLI + MTX to Day +52 | MMRD: 4 x 10^4/kg DLI + MTX to Day +52 | MMRD: 4 x 10^4/kg DLI + MTX to Day +80 | MMRD: 5 x 10^4/kg DLI + MTX to Day +80 | MUD: 3 x 10^4/kg DLI + MTX to Day +24 | MUD: 3 x 10^4/kg DLI + MTX to Day +52 |
|---|---|---|---|---|---|---|---|
| Number of Participants With Immune Recovery Following Transplantation | 1 | 1 | 1 | 4 | 6 | 1 | 1 |
Patients were evaluated for acute GVHD due to prophylactic DLI between the day of prophylactic DLI infusion and Day +180 after transplant. GVHD was graded using standard criteria.
| Participants | MMRD: 3 x 10^4/kg DLI + MTX to Day +24 | MMRD: 3 x 10^4/kg DLI + MTX to Day +52 | MMRD: 4 x 10^4/kg DLI + MTX to Day +52 | MMRD: 4 x 10^4/kg DLI + MTX to Day +80 | MMRD: 5 x 10^4/kg DLI + MTX to Day +80 | MUD: 3 x 10^4/kg DLI + MTX to Day +24 | MUD: 3 x 10^4/kg DLI + MTX to Day +52 |
|---|---|---|---|---|---|---|---|
| No GVHD/ Grade I GVHD | 2 | 1 | 1 | 9 | 8 | 1 | 1 |
| Grade II GVHD | 0 | 1 | 1 | 1 | 1 | 0 | 0 |
| Grade III/IV GVHD | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Subjects were actively monitored for adenovirus, cytomegalovirus (CMV), human herpes virus 6 (HHV6), and Epstein-Barr virus (EBV) as part of standard post-transplant care. All infections were collected from date of DLI until 1 year after transplant.
| participants | Infusion of Donor Lymphocytes |
|---|---|
| HHV-6 reactivation, no disease | 18 |
| Viral upper respiratory infections | 17 |
| Adenovirus reactivation, no disease | 11 |
| Clostridium difficile colitis | 9 |
| Sinusitis | 8 |
| CMV reactivation, no disease | 5 |
| Galactomannan positive | 5 |
| BK virus, no disease | 5 |
| BK virus, hemorrhagic cystitis | 4 |
| EBV-related lymphoproliferative disease | 4 |
| Bacteremia, gram negative | 4 |
| Herpes simplex virus | 4 |
| Bacteremia, gram positive | 4 |
| Acute otitis media | 3 |
| Candidiasis (non-invasive) | 3 |
| Pneumonia | 3 |
| Infection with normal ANC - grade 3 | 3 |
| Adenovirus disease | 2 |
| EBV reactivation, no disease | 2 |
| Varicella | 2 |
| Nocardia | 2 |
| Pneumonia- fungal | 1 |
| Methicillin-resistant staphylococcus aureus (MRSA) | 1 |
| Norovirus | 1 |
| Parvovirus B19 (low level) | 1 |
| Rotavirus | 1 |
| Sapovirus | 1 |
| Possible respiratory fungal infection (rhizomucor) | 1 |
Collected over From the time of donor lymphocyte infusion (DLI) up to one year after transplant.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Infusion of Donor Lymphocytes | 12/38 (31.6%) | 32/38 (84.2%) | 27/38 (71.1%) |
| Event | Infusion of Donor Lymphocytes |
|---|---|
| FeverGeneral disorders | 24/38 |
| HHV-6 reactivationInfections and infestations | 6/38 |
| Graft vs Host diseaseImmune system disorders | 5/38 |
| EBV-related lymphoproliferative diseaseInfections and infestations | 4/38 |
| RelapseNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/25 |
| PneumoniaInfections and infestations | 3/38 |
| GastroenteritisInfections and infestations | 3/38 |
| CMV reactivationInfections and infestations | 2/38 |
| Infection w/ unknown absolute neutrophil count (ANC)Infections and infestations | 2/38 |
| Thrombotic MicroangiopathyBlood and lymphatic system disorders | 2/38 |
| Event | Infusion of Donor Lymphocytes |
|---|---|
| NeutropeniaInvestigations | 12/38 |
| Platelet count decreasedInvestigations | 10/38 |
| RelapseNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 6/25 |
| LeukopeniaInvestigations | 8/38 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 5/38 |
| RashSkin and subcutaneous tissue disorders | 4/38 |
| Thrombotic microangiopathyBlood and lymphatic system disorders | 3/38 |
| Thrombotic microangiopathyBlood and lymphatic system disorders | 3/38 |
| LymphopeniaInvestigations | 3/38 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 3/38 |
| Age, Customized(participants) | Infusion of Donor Lymphocytes |
|---|---|
| < 1 year | 2 |
| 1-2 years | 3 |
| 2-4 years | 3 |
| 4-6 years | 3 |
| 6-8 years | 3 |
| 8-10 years | 3 |
| 10-12 years | 4 |
| 12-14 years | 4 |
| 14-16 years | 3 |
| 16-18 years | 6 |
| > 18 years | 4 |
| Sex: Female, Male(Participants) | Infusion of Donor Lymphocytes |
|---|---|
| Female | 16 |
| Male | 22 |
| Race/Ethnicity, Customized(Participants) | Infusion of Donor Lymphocytes |
|---|---|
| Caucasian | 8 |
| African American | 19 |
| Hispanic or Latino | 10 |
| Other | 1 |
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Immunologic Deficiency Syndromes→
Wake Forest University Health Sciences