A Phase 2 interventional study of Cyclophosphamide and Busulfan in Core Binding Factor Alpha Subunits, Hematologic Neoplasms and Leukemia, sponsored by National Cancer Institute (NCI). Not yet recruiting at 1 site in United States. Open to participants aged 4 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
Background:
Some blood cancers can be caused by germline variants (changes) in a person s RUNX1 gene. Germline variants are genetic inherited changes a person is born with. Stem cell transplants are used to treat many diseases including blood cancers. Stem cell transplantation for patients with germline RUNX1 mutation driven blood cancers is standard of care and available in most major medical centers. The difference with this transplantation protocol is that it is prospective, only available to participants with germline RUNX1 variants and designed to determine the extent to which tailoring chemotherapy and supportive care medication doses for each individual patient may improve outcomes compared to data derived from retrospective transplantation protocols for patients with RUNX1 varinats which is less accurate.
Objective:
The primary objective of this protocol is to determine how tailored doses of chemotherapy and supportive care medications may improve disease free survival as compared to historical/expected disease free survival.
Eligibility:
People aged 4 to 70 years with blood cancer caused by a RUNX1 gene mutation. Other participants are also needed: (1) stem cell donors; (2) relatives who do not have a mutation in the RUNX1 gene; and (3) healthy volunteers.
Design:
Participants with blood cancer will be screened during approximately 1-3 months before transplatation. They will have blood tests and tests of their heart and lung function. A sample of bone marrow may be taken.
A flexible tube (central line) will be inserted into a vein in participants' chest or lower neck. This line will remain in place during the hospitalization and be used to draw blood and administer drugs. These lines are almost always transitioned to a peripherally inserted central catheter (PICC) line at the time of hospital discharge.
Participants will be inpatient for 4 to 5 weeks. They will receive drugs to prepare their body for the stem cell transplant. Some may also receive radiation treatment. Other tests will include imaging scans. The stem cell transplant will be given through the central line.
After discharge from the clinic, participants will have follow-up visits at least once per week for approximately 100 days. Then they will have follow-up clinic visits for 3 years.
Donors, relatives, and healthy volunteers may provide samples of blood, stool, and saliva. Adults may also opt to provide samples of skin and bone marrow.
Background:
Objective:
-To determine the proportion of participants with disease free survival (DFS) at 1 year post haploidentical transplantation.
Eligibility:
Affected participants (Recipients)
Unaffected participants
Haploidentical donors
---Age >= 4 years
Family members and healthy volunteers
Design:
Participants in the affected Cohort will be divided into two conditioning Arms prior to receiving a HSCT at day 0
1,444 studies on the registry are indexed under Hematologic Neoplasms; 420 are open to participants now.
This study's planned enrollment of 102 is above the median of 46 across 1,044 interventional studies indexed under Hematologic Neoplasms.
Browse Hematologic Neoplasms studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) 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.
Affected participants (Recipients)
Subjects requiring standard therapies to prepare for HCT should ideally be referred to this study in remission, if possible. However, sometimes disease status changes during evaluation for HCT and it is necessary to establish disease control through the administration of standard therapies (e.g. hypomethylating agents or menin inhibitors if indicated) during evaluation for HCT. If ongoing therapy for the underlying disease outside of the NIH is not in the best interest of the subject according to the clinical judgment of the NIH PI, then the subject may receive standard treatment for his/her underlying hematologic malignancy as a bridge to HCT on this protocol, prior to starting the research phase of the study. If it becomes apparent that the subject will not be able to proceed to HCT, then he/she must come off study. Subjects receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol.
as follows:
---Women of (WOCBP) must agree to use highly effective contraception (hormonal, intrauterine device [IUD], abstinence, surgical sterilization) at the study entry and up to and 12 months post conditioning and/or post-transplant.
Additional criteria for recipients suitable for MAC
Recipients must have adequate organ function as defined below:
Additional criteria for recipients suitable for RIC
Recipients must have adequate organ function as defined below:
Unaffected participants
Haploidentical donors
----Age >=4 years
Unaffected family members
EXCLUSION CRITERIA:
-All participants
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.
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.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
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.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
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.
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.
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.
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.
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.
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.
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.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
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.
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.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
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.
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.
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.
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.
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.
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.
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.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Myeloablative conditioning with cyclophosphamide and busulfan followed by hematopoietic stem cell transplant
Drug: Cyclophosphamide · Drug: Busulfan · Biological: Hematopoietic stem cells · Drug: Tacrolimus · Drug: Mycophenolate Mofetil
Reduced intensity conditioning with fludarabine, cyclophosphamide and total body irradiation followed by hematopoietic stem cell transplant
Drug: Cyclophosphamide · Drug: Fludarabine · Radiation: Total Body Irradiation · Biological: Hematopoietic stem cells · Drug: Tacrolimus · Drug: Mycophenolate Mofetil
Biospecimen Collection
For Arm 1 myeloablative conditioning, given on days -6 and -5 at 50 mg/kg/day IV. For Arm 2 reduced intensity conditioning, give on day -5 and day -4 at 14.5 mg/kg IV once daily. GVHD prophylaxis for all recipients, 50mg/kg IV on Day 3 and Day 4 post HSCT.
For Arm 1 myeloablative conditioning, given on day -4 to day -1. The daily busulfan area under the curve goal is 4263-4872 mcMolar x min daily or 17.5-20 mg/hr/L per day (70-80 mg\*hr/L over 4 days).
For Arm 2 reduced intensity conditioning, given once daily on days -5 through day -2. The cumulative fludarabine area under the curve is 20 mg\*hr/mL
Form Arm 2 reduced intensity conditioning, total 4 Gy, fractionated 2 Gy twice per day, given on day -1.
Given on Day 0. The target dose is any dose \> or equal to 7 x 10\^6 and \<= 10 x 10\^6 CD34+ cells/kg recipient body weight.
GVHD prophylaxis for all recipients. Given intravenously at a dose of .02 mg/kg from Day 5 until Day 100.
GVHD prophylaxis for all recipients. Given at a dose of 15 mg/kg three times a day from Day 5 through Day 35.
To determine the proportion of participants with disease free survival at 1 year post haploidentical transplantation.
The proportion of participants with disease-free survival (DFS) at one year post transplantation will be reported separately by treatment arm along with 80% and 95% two-sided confidence intervals.
Time frame: 1 year post HSCT
To determine the overall survival and non-relapsed mortality at years 1, 2 and 3 post haploidentical transplantation.
OS will be evaluated using a Kaplan-Meier curve for all evaluable participants beginning at their date of transplant, along with the median value and the 95% confidence interval at the median, separately by treatment arm. Participants who are lost to follow-up will be censored in the data analysis at the time when they become unfollowable for OS. NRM will be evaluated using a cumulative incidence curve by treatment arm, with relapse mortality as the competing risk for NRM. The cumulative incidence of NRM will be reported at year 1 and if applicable at years 2 and 3.
Time frame: Assessed daily during initial HSCT hospitalization, at D30, 60, 100, 180, and then yearly until year 3 post HSCT.
To determine the incidence and severity of Grade II-IV and III-IV aGVHD at Days 100 and 180 and severe cGVHD at 1 year post haploidentical transplantation.
The cumulative incidence curves for aGVHD (Grades II-IV and III-IV) and for severe cGVHD will be constructed separately by treatment arm, along with aGVHD and cGVHD as competing risks. The cumulative incidence of aGVHD Grades II-IV and III-IV will be reported at D100 and D180 and that for cGVHD will be reported at year 1.The incidence and severity of aGVHD at D100 and D180 will also be evaluated by reporting the proportion of participants with aGVHD Grades II-IV and III-IV along with the corresponding 95% two-sided confidence intervals by arm. Likewise, the proportion of participants with cGVHD will be reported at year 1 by arm along with a 95% confidence interval.
Time frame: Cumulative incidence curves for aGVHD and cGVHD will be evaluated daily during hospitalization, and at D30, 60, 100, 180, and 360 post HSCT. The proportion of participants having cGVHD will be reported at year 1 post HSCT.
To determine the disease-free survival and event-free survival for up to year 3 post haploidentical transplantation.
The Kaplan-Meier curves for all evaluable participants beginning at their transplant date may be applied to evaluate the DFS and EFS 3, along with the corresponding median values and the 95% confidence intervals at the medians, separately by arm, if applicable. In addition, the proportions of participants may be reported at year 2 and year 3 for DFS and years 1, 2, and 3 for EFS, if applicable, along with corresponding 95% confidence intervals.
Time frame: Assessed by bone marrow biopsy and chemistry tests daily during initial HSCT hospitalization, and at D30, 60, 100, 180, and then yearly until year 3 post HSCT.
Plan to share: Yes — This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
Access criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.
Start is estimated for Nov 2026; primary completion for Jun 2033, 78 months later.
Of 114 non-industry phase 2 interventional studies under Hematologic Neoplasms, half reached primary completion within 59 months of starting (the median), counting those still running; a quarter within 42 and three quarters within 95. This study's planned 78 months is above that.
Counting every sponsor, half of 136 studies reached it within 57 months; a quarter within 40 and three quarters within 94.
Start moved 32 times since we started tracking on Sep 25, 2026: Sep 2026 → Nov 2026, last on Nov 10, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Nov 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Cyclophosphamide · Busulfan · Fludarabine · Hematopoietic Stem Cell · Tacrolimus · Mycophenolic Acid
National Cancer Institute (NCI) →