A Phase 2/3 interventional study of Stem cell transplant and Fludarabine monophosphate in Diamond-Blackfan Anemia, Kostmann's Neutropenia and Shwachman-Diamond Syndrome, sponsored by Masonic Cancer Center, University of Minnesota. Completed at 1 site in United States. Open to participants aged Up to 35 Years. Per ClinicalTrials.gov, last updated 2017-12-28.
Sponsored by Masonic Cancer Center, University of Minnesota · Phase 2/3, Interventional, and Treatment
The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders.
Prior to transplantation, subjects will receive the drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation.
Those patients receiving donor marrow will have the T cells (a type of white blood cell in the donor marrow) removed to lower the risk that the new marrow will react to their body, a condition called Graft-Versus-Host-Disease (GVHD). After bone marrow transplantation, subjects will receive drugs to help prevent GVHD, including cyclosporin and mycophenolate mofetil (MMF).
Blood samples are taken at day 28, day 60, day 100, 1 year and as required by medical status yearly for five years after transplant to evaluate how well the new marrow is growing. A bone marrow biopsy is required at day 21, at day 100 and 1 year.
56 studies on the registry are indexed under Anemia, Diamond-Blackfan; 10 are open to participants now.
This study's enrollment of 10 is below the median of 28 across 44 interventional studies indexed under Anemia, Diamond-Blackfan.
Browse Anemia, Diamond-Blackfan studies →Masonic Cancer Center, University of Minnesota is the lead sponsor of 286 studies on the registry; 35 are open to participants now.
Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients eligible for transplantation under this protocol will be \<35 years of age, and will be diagnosed with:
Diamond Blackfan Anemia:
Kostmann's Neutropenia, Shwachman-Diamond syndrome:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome
Procedure: Stem cell transplant · Drug: Fludarabine monophosphate · Procedure: Total lymphoid irradiation · Drug: Busulfan · Biological: anti-thymocyte globulin
Stem cell transplant on Day 0 - healthy marrow from an unrelated individual. A minimum of 1.0 x 10\^9/kg nucleated cells/kg ideal body weight will be collected with a goal of 2.0 x 10\^9/kg.
Also known as: BMT
fludarabine 175 mg/m\^2 (total) on Days -6 through -3.
Also known as: Fludara
Dose 500 cGy radiation therapy to specific areas of the body
Also known as: TLI
Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter),
Also known as: Busulfex
anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter
Also known as: ATG
Number of Patients Alive (Survival) at 2 Years
Calculated from day 1 of transplant to last contact.
Time frame: 2 years
Number of Patients Alive at Three Years (Survival)
Number of subjects who survived 3 years post-transplant.
Time frame: 3 years
Number of Patients With Succcessful Engraftment After Transplantation
Number of patients who received non-genotypic identical marrow or cord blood cells using a "non-myeloablative" preparative regimen and exhibited engraftment at Day 42.
Time frame: 42 Days
Number of Patients With Grade 2-4 Acute Graft Versus Host Disease
Number of patients with Grade 2, 3 and 4 Acute (normally observed within the first 100 days) Graft Versus Host Disease. Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GVHD usually have a poor prognosis. Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening.
Time frame: 100 Days
Number of Patients With Chronic Graft Versus Host Disease
Number of patients who exhibited chronic (normally occurs after 100 days) Graft Versus Host Disease at 2 years post transplant. Chronic graft-versus-host-disease, over its long-term course, can also cause damage to the connective tissue and exocrine glands.
Time frame: 2 years
Number of Patients With Disease Recurrence
Number of patients who exhibited disease recurrence at 2 years.
Time frame: 2 years
| Milestone | Bone Marrow Failure Patients |
|---|---|
| Started | 10 |
| Completed | 10 |
| Not completed | 0 |
Calculated from day 1 of transplant to last contact.
| Participants | Bone Marrow Failure Patients |
|---|---|
| Number of Patients Alive (Survival) at 2 Years | 6 |
Number of subjects who survived 3 years post-transplant.
| Participants | Bone Marrow Failure Patients |
|---|---|
| Number of Patients Alive at Three Years (Survival) | 6 |
Number of patients who received non-genotypic identical marrow or cord blood cells using a "non-myeloablative" preparative regimen and exhibited engraftment at Day 42.
| Participants | Bone Marrow Failure Patients |
|---|---|
| Number of Patients With Succcessful Engraftment After Transplantation | 10 |
Number of patients with Grade 2, 3 and 4 Acute (normally observed within the first 100 days) Graft Versus Host Disease. Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GVHD usually have a poor prognosis. Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening.
| Participants | Bone Marrow Failure Patients |
|---|---|
| Number of Patients With Grade 2-4 Acute Graft Versus Host Disease | 5 |
Number of patients who exhibited chronic (normally occurs after 100 days) Graft Versus Host Disease at 2 years post transplant. Chronic graft-versus-host-disease, over its long-term course, can also cause damage to the connective tissue and exocrine glands.
| Participants | Bone Marrow Failure Patients |
|---|---|
| Number of Patients With Chronic Graft Versus Host Disease | 3 |
Number of patients who exhibited disease recurrence at 2 years.
| Participants | Bone Marrow Failure Patients |
|---|---|
| Number of Patients With Disease Recurrence | 0 |
Collected over Day 1 of study up through 1 year. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bone Marrow Failure Patients | — | 5/10 (50%) | 0/10 (0%) |
| Event | Bone Marrow Failure Patients |
|---|---|
| Bone marrow graft failureBlood and lymphatic system disorders | 3/10 |
| DeathGeneral disorders | 3/10 |
| Graft-versus-host disease (acute)Blood and lymphatic system disorders | 1/10 |
| Age, Categorical(Participants) | Bone Marrow Failure Patients |
|---|---|
| <=18 years | 10 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age, Continuous(years) | Bone Marrow Failure Patients |
|---|---|
| Mean | 4.8 ± 7.6 |
| Sex: Female, Male(Participants) | Bone Marrow Failure Patients |
|---|---|
| Female | 3 |
| Male | 7 |
| Region of Enrollment(participants) | Bone Marrow Failure Patients |
|---|---|
| United States | 10 |
This study is completed, as verified in Dec 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Fludarabine phosphate · Busulfan · Antilymphocyte Serum
Masonic Cancer Center, University of Minnesota →