A Phase 2 interventional study of Alemtuzumab and Busulfan in Myeloid Malignancy, Bone Marrow Failure Syndrome and Transfusion-dependent Red Blood Cell (RBC) Defect, sponsored by University of California, San Francisco. Terminated at 1 site in United States. Open to participants aged 3 Months to 30 Years. Per ClinicalTrials.gov, last updated 2020-02-26.
Sponsored by University of California, San Francisco · Phase 2, Interventional, and Treatment
The purpose of this study is to find out what effects, good and/or bad, the addition of clofarabine, a new chemotherapy agent, to a standard busulfan and fludarabine conditioning treatment has. The study will also look at what causes some people to have high drug levels of these medications in their body compared to other people that may have low drug levels even if they all receive the same dose of medication.
91 studies on the registry are indexed under Bone Marrow Failure Disorders; 29 are open to participants now.
This study's enrollment of 16 is below the median of 26 across 69 interventional studies indexed under Bone Marrow Failure Disorders.
Browse Bone Marrow Failure Disorders studies →University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.
Of its 267 completed or terminated interventional studies of FDA-regulated products, 202 (76%) 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.
Stratum A: Non-Malignant Diseases, including:
Stratum B: Myeloid , including:
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.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
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.
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.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
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.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
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.
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.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
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.
Drug: Busulfan · Drug: Fludarabine · Drug: Clofarabine
Drug: Alemtuzumab · Drug: Busulfan · Drug: Fludarabine · Drug: Clofarabine
0.5 mg/kg (max 15 mg or max 6 mg), IV, Day -12 to Day -10 pre-HCT
Also known as: Campath
0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT
Also known as: Busulfex
40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
Also known as: Fludara
10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
Also known as: Clolar
Number of Participants With Treatment-Related Adverse Events as a Measure of Safety and Tolerability
Severe Toxicity will be defined as death or Grade IV by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 pulmonary or hepatic failure (including moderate veno-occlusive disease(VOD) related to the transplant conditioning regimen within 100 days post-HCT. VOD will be defined by standard criteria. Patients must have Bilirubin \>2.0 plus Hepatomegaly and/or Right upper quadrant (RUQ) pain plus Weight gain \>5%.
Time frame: Up to 5 years on average
Engraftment Rate of Patients With Non-malignant Diseases (Stratum A)
Engraftment will be defined as the development of an Absolute Neutrophil Count (ANC) \>500 for 3 consecutive days plus donor CD14/15 cells \>70%. The engraftment rate in the population used for historical control is 40%. If 3 patients in Stratum A experience graft rejection, this stratum will close early for failing to achieve superior engraftment compared to standard-of-care.
Time frame: Participants will have engraftment blood studies starting approximately Day 30 post hematopoietic stem cell transplant and then monthly until stable. Average study participation is approximately 5 years.
Mixed-donor Chimerism Rate of Patients With High-risk Myeloid Malignancies (Stratum B)
Full-donor chimerism will be defined by as ≥99% donor cells by Short Tandem Repeat (STR) analysis in all cell lines (CD3, CD14/15, and CD19) in peripheral blood. The historic control for Stratum B was determined using the 20 patients who were transplanted from 2005 - 2010 with Busulfan (BU)-based regimens and who retrospectively would have been eligible for the current trial. Of these 20 patients, at 100 days post-HCT, only 8 (40%) patients had full-donor chimerism. If 5 patients in Stratum B experienced mixed-donor chimerism at Day 100, we will close this stratum early for failing to achieve superior donor cell engraftment compared to standard-of-care.
Time frame: Participants will have peripheral blood chimerism assessed at Day 100 post hematopoietic stem cell transplant and then monthly until stable.
Serum Concentrations and Potential for Drug-drug Interaction of Fludarabine and Clofarabine
Fludarabine and clofarabine drug levels and potential covariates influencing drug exposure such as renal function and genetic variants involved in drug metabolism, distribution, and activation will be analyzed using standard population pharmacokinetic methods using non-linear mixed effects modeling (NONMEM) software
Time frame: Pharmacokinetics (PK) blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant.
| Milestone | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies |
|---|---|---|
| Started | 10 | 6 |
| Completed | 10 | 6 |
| Not completed | 0 | 0 |
Severe Toxicity will be defined as death or Grade IV by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 pulmonary or hepatic failure (including moderate veno-occlusive disease(VOD) related to the transplant conditioning regimen within 100 days post-HCT. VOD will be defined by standard criteria. Patients must have Bilirubin \>2.0 plus Hepatomegaly and/or Right upper quadrant (RUQ) pain plus Weight gain \>5%.
| participants | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies |
|---|---|---|
| Death | 1 | 0 |
| Veno-occlusive disease(VOD) | 1 | 1 |
Engraftment will be defined as the development of an Absolute Neutrophil Count (ANC) \>500 for 3 consecutive days plus donor CD14/15 cells \>70%. The engraftment rate in the population used for historical control is 40%. If 3 patients in Stratum A experience graft rejection, this stratum will close early for failing to achieve superior engraftment compared to standard-of-care.
| percentage of participants | Stratum A: Patients With Non-Malignancies |
|---|---|
| Engraftment Rate of Patients With Non-malignant Diseases (Stratum A) | 66.67 |
Full-donor chimerism will be defined by as ≥99% donor cells by Short Tandem Repeat (STR) analysis in all cell lines (CD3, CD14/15, and CD19) in peripheral blood. The historic control for Stratum B was determined using the 20 patients who were transplanted from 2005 - 2010 with Busulfan (BU)-based regimens and who retrospectively would have been eligible for the current trial. Of these 20 patients, at 100 days post-HCT, only 8 (40%) patients had full-donor chimerism. If 5 patients in Stratum B experienced mixed-donor chimerism at Day 100, we will close this stratum early for failing to achieve superior donor cell engraftment compared to standard-of-care.
| percentage of participants | Stratum B: Patients With Myeloid Malignancies |
|---|---|
| Mixed-donor Chimerism Rate of Patients With High-risk Myeloid Malignancies (Stratum B) | 66.67 |
Fludarabine and clofarabine drug levels and potential covariates influencing drug exposure such as renal function and genetic variants involved in drug metabolism, distribution, and activation will be analyzed using standard population pharmacokinetic methods using non-linear mixed effects modeling (NONMEM) software
No measurements were reported for this outcome.
Collected over Up to 5 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stratum A: Patients With Non-Malignancies | 1/10 (10%) | 1/10 (10%) | 10/10 (100%) |
| Stratum B: Patients With Myeloid Malignancies | 6/6 (100%) | 1/6 (16.7%) | 6/6 (100%) |
| Event | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies |
|---|---|---|
| Veno-occlusive disease (VOD)General disorders | 1/10 | 1/6 |
| Event | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies |
|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 10/10 | 6/6 |
| AnemiaBlood and lymphatic system disorders | 10/10 | 6/6 |
| Mucositis oralGastrointestinal disorders | 10/10 | 6/6 |
| Lung InfectionInfections and infestations | 0/10 | 1/6 |
| Lymph Gland InfectionInfections and infestations | 0/10 | 1/6 |
| StridorRespiratory, thoracic and mediastinal disorders | 1/10 | 0/6 |
| Age, Customized(Participants) | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies | Total |
|---|---|---|---|
| 0-9 years old | 10 | 6 | 16 |
| Sex: Female, Male(Participants) | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies | Total |
|---|---|---|---|
| Female | 4 | 0 | 4 |
| Male | 6 | 6 | 12 |
| Ethnicity (NIH/OMB)(Participants) | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies | Total |
|---|---|---|---|
| Hispanic or Latino | 4 | 0 | 4 |
| Not Hispanic or Latino | 6 | 6 | 12 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 2 | 2 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 7 | 3 | 10 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | Stratum A: Patients With Non-Malignancies | Stratum B: Patients With Myeloid Malignancies | Total |
|---|---|---|---|
| United States | 10 | 6 | 16 |
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drugs tested here: Busulfan · Fludarabine · Clofarabine
Bone Marrow Failure Disorders →
University of California, San Francisco →