A Phase 2 interventional study of Busulfan and Cyclophosphamide in Anemia, ASXL1 Gene Mutation and EZH2 Gene Mutation, sponsored by University of Utah. Terminated at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2022-05-05.
Sponsored by University of Utah · Phase 2, Interventional, and Treatment
This phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and cyclophosphamide in treating participants with multiple myeloma or myelofibrosis. Drugs used in chemotherapy, such as busulfan, fludarabine, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving busulfan and fludarabine before and cyclophosphamide after donor stem cell may work better in treating participants with multiple myeloma or myelofibrosis.
PRIMARY OBJECTIVES:
I. To evaluate non-relapse mortality (NRM) up to day +100.
SECONDARY OBJECTIVES:
I. To evaluate non-relapse mortality (NRM) up to day +365. II. To evaluate the incidence of acute graft versus host disease (GVHD) and chronic GVHD up to day +365 post-transplant.
III. To evaluate the overall survival and disease free survival up to 1 year. IV. To evaluate clinical response and molecular response (complete response and partial response) up to 1 year.
OUTLINE:
Participants receive busulfan intravenously (IV) over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic cell transplantation (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
After completion of study treatment, participants are followed up for 1 year.
1,810 studies on the registry are indexed under Anemia; 215 are open to participants now.
This study's enrollment of 6 is below the median of 117 across 1,336 interventional studies indexed under Anemia.
Browse Anemia studies →University of Utah is the lead sponsor of 994 studies on the registry; 175 are open to participants now.
Of its 114 completed or terminated interventional studies of FDA-regulated products, 69 (61%) 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.
Participants must have documented multiple myeloma (MM)
Participants must have histologically documented myelofibrosis (MF)
Subset of intermediate stage 1 participants; defined by:
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 scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
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.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
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.
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.
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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
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.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
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.
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.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Procedure: Hematopoietic Cell Transplantation · Other: Laboratory Biomarker Analysis
Given IV
Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Given IV
Also known as: Fluradosa
Undergo HSCT
Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantation
Correlative studies
Non-relapse Mortality (NRM) at Day 100
NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
Time frame: Up to day 100
Non-relapse Mortality (NRM) at Day 365
NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
Time frame: Up to day 365
Incidence of Acute Graft Versus Host Disease (GVHD)
Cases of acute graft versus host disease (GVHD) will be diagnosed by the treating physician and will be reported as a count of participants with acute GVHD.
Time frame: Up to day 365
Incidence of Chronic GVHD
Chronic GVHD will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. This will be reported as a count of participants diagnosed with chronic GVHD
Time frame: Up to day 365
Overall Survival at One Year
Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.
Time frame: Up to 1 year
Disease Free Survival at One Year
Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.
Time frame: Up to 1 year
Number of Participants With Different Clinical Responses
Clinical Responses were determined by disease-specific criteria taking into account multiple clinical and molecular markers. Multiple Myeloma (MM) response was determined using International Myeloma Working Group (IMWG) consensus criteria for response. Participants with MM had either Stringent Complete Response (sCR) or Very Good Partial Response (VGPR). Myelofibrosis (MF) response was determined using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus criteria. Participants with MF had either Complete Response (CR) or Stable Disease (SD) (also referred to in the protocol as no response).
Time frame: Up to 1 year
Number of Participants With Minimal Residual Disease (MRD) Response
After bone marrow transplant, bone marrow was collected every 3-6 months (as clinically indicated per treating investigator) for up to one year after bone marrow transplant. Bone marrow was evaluated by a clinical pathologist for any evidence of multiple myeloma (MM) or myelofibrosis (MF). Evidence of MM or MF in the bone marrow is referred to as minimal residual disease (MRD). A participant with evidence of MRD is MRD-positive. A participant with no evidence of MRD is MRD-negative, which is considered an MRD response. This outcome reports the number participants with MRD responses any time between bone marrow transplant up to one year of follow-up.
Time frame: Up to 1 year
| Milestone | All Particpants - Treatment |
|---|---|
| Started | 6 |
| Completed | 6 |
| Not completed | 0 |
NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
| Participants | All Participants - Treatment |
|---|---|
| Non-relapse Mortality (NRM) at Day 100 | 1 |
NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
| Participants | All Participants - Treatment |
|---|---|
| Non-relapse Mortality (NRM) at Day 365 | 2 |
Cases of acute graft versus host disease (GVHD) will be diagnosed by the treating physician and will be reported as a count of participants with acute GVHD.
| Participants | All Particpants - Treatment |
|---|---|
| Incidence of Acute Graft Versus Host Disease (GVHD) | 2 |
Chronic GVHD will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. This will be reported as a count of participants diagnosed with chronic GVHD
| Participants | All Particpants - Treatment |
|---|---|
| Incidence of Chronic GVHD | 1 |
Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.
| Participants | All Particpants - Treatment |
|---|---|
| Overall Survival at One Year | 3 |
Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.
| Participants | All Particpants - Treatment |
|---|---|
| Disease Free Survival at One Year | 3 |
Clinical Responses were determined by disease-specific criteria taking into account multiple clinical and molecular markers. Multiple Myeloma (MM) response was determined using International Myeloma Working Group (IMWG) consensus criteria for response. Participants with MM had either Stringent Complete Response (sCR) or Very Good Partial Response (VGPR). Myelofibrosis (MF) response was determined using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus criteria. Participants with MF had either Complete Response (CR) or Stable Disease (SD) (also referred to in the protocol as no response).
| Participants | All Particpants - Treatment |
|---|---|
| Stringent Complete Response (sCR) | 1 |
| Very Good Partial Response (VGPR) | 1 |
| Complete Response (CR) | 2 |
| Stable Disease (SD) | 1 |
After bone marrow transplant, bone marrow was collected every 3-6 months (as clinically indicated per treating investigator) for up to one year after bone marrow transplant. Bone marrow was evaluated by a clinical pathologist for any evidence of multiple myeloma (MM) or myelofibrosis (MF). Evidence of MM or MF in the bone marrow is referred to as minimal residual disease (MRD). A participant with evidence of MRD is MRD-positive. A participant with no evidence of MRD is MRD-negative, which is considered an MRD response. This outcome reports the number participants with MRD responses any time between bone marrow transplant up to one year of follow-up.
| Participants | All Particpants - Treatment |
|---|---|
| Number of Participants With Minimal Residual Disease (MRD) Response | 5 |
Collected over Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All Participants - Treatment | 3/6 (50%) | 4/6 (66.7%) | 5/6 (83.3%) |
| Event | All Participants - Treatment |
|---|---|
| Lung infectionInfections and infestations | 2/6 |
| Acute kidney injuryRenal and urinary disorders | 1/6 |
| Blood and lymphatic system disorders - OtherBlood and lymphatic system disorders | 1/6 |
| Death NOSGeneral disorders | 1/6 |
| DiarrheaGastrointestinal disorders | 1/6 |
| Hepatobiliary disorders - OtherHepatobiliary disorders | 1/6 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 1/6 |
| SepsisInfections and infestations | 1/6 |
| Sinus disorderRespiratory, thoracic and mediastinal disorders | 1/6 |
| Event | All Participants - Treatment |
|---|---|
| HypokalemiaMetabolism and nutrition disorders | 2/6 |
| AnemiaBlood and lymphatic system disorders | 1/6 |
| Blood bilirubin increasedInvestigations | 1/6 |
| Creatinine increasedInvestigations | 1/6 |
| HypophosphatemiaMetabolism and nutrition disorders | 1/6 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 1/6 |
| InsomniaPsychiatric disorders | 1/6 |
| HypomagnesemiaMetabolism and nutrition disorders | 1/6 |
| SyncopeNervous system disorders | 1/6 |
| Urinary tract infectionInfections and infestations | 1/6 |
| Age, Categorical(Participants) | All Participants - Treatment |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 5 |
| >=65 years | 1 |
| Age, Continuous(years) | All Participants - Treatment |
|---|---|
| Mean | 56.17 ± 6.97 |
| Age, Continuous(years) | All Participants - Treatment |
|---|---|
| Median | 54.5 (50 to 69) |
| Sex: Female, Male(Participants) | All Participants - Treatment |
|---|---|
| Female | 5 |
| Male | 1 |
| Ethnicity (NIH/OMB)(Participants) | All Participants - Treatment |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 5 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | All Participants - Treatment |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 6 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
This study is terminated, as verified in May 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Busulfan · Cyclophosphamide · Fludarabine