Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers

NCT07524530 | Not Yet Recruiting Phase 2

• 2 other identifiers: 10002233002233-C
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Core Binding Factor Alpha Subunits; Hematologic Neoplasms; Leukemia; Lymphoma

Keywords

RUNX1; Haploidentical Hematopoietic Stem Cell Transplant; Germline RUNX1; germline RUNX1-aassociated myeloid malignancy

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year post HSCT

Secondary Outcomes (3)

• To determine the overall survival and non-relapsed mortality at years 1, 2 and 3 post haploidentical transplantation.

  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.

  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.

  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.

Study Arms (3)

Arm 1

EXPERIMENTAL

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

Arm 2

EXPERIMENTAL

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

Arm 3

NO INTERVENTION

Biospecimen Collection

Interventions

Hematopoietic stem cells BIOLOGICAL

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.

Arm 1; Arm 2

Tacrolimus DRUG

GVHD prophylaxis for all recipients. Given intravenously at a dose of .02 mg/kg from Day 5 until Day 100.

Arm 1; Arm 2

Mycophenolate Mofetil DRUG

GVHD prophylaxis for all recipients. Given at a dose of 15 mg/kg three times a day from Day 5 through Day 35.

Arm 1; Arm 2

Cyclophosphamide DRUG

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.

Arm 1; Arm 2

Busulfan DRUG

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).

Arm 1

Fludarabine DRUG

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

Arm 2

Total Body Irradiation RADIATION

Form Arm 2 reduced intensity conditioning, total 4 Gy, fractionated 2 Gy twice per day, given on day -1.

Arm 2

Eligibility Criteria

• Age: 4 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Affected participants (Recipients)
• History of deleterious or suspected deleterious (defined as P/LP or VUS with RUNX1 phenotype) germline RUNX1 mutation as defined by ClinVar (nih.gov)
• Histological confirmation of a myeloid malignancy - acute or chronic leukemia (\<5% marrow blasts preferred) or myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) (\<10% marrow blasts preferred). Participants may be treated on this study to achieve preferred blast cutoffs. Participants with poorly responsive or relapsed disease remain eligible and may proceed as the graft-versus-leukemia (GVL) effect may produce cures.
• 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 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.
• Availability of a haploidentical donor (HLA-match only).
• Age \>= 4 and \<= 70 years
• Karnofsky (\>=16 years) or Lansky (\<16 years) \>=60%
• For human immunodeficiency virus (HIV)-infected participants, participant must be on effective anti-retroviral therapy, without uncontrolled opportunistic infection and have approval via Transplant Infectious Disease consultation. Consider donor with CCR5(delta)32 homozygosity for these participants.
• For individuals with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load (VL) must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV VL.
• Contraception as follows:
• Women of child-bearing potential (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.
• Men that can father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 12 months posttransplant or 4 months after conditioning if transplant is not done. We also will recommend men that can father children with partners that can bear children ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men that can father children must not freeze or donate sperm within the same period.
• Breastfeeding participants must be willing to discontinue breastfeeding during the study and for 12 months post-transplant or 1 week after conditioning if transplant is not done.
• Willingness to remain in the NIH hospital or, if discharged, stay close to the NIH (30 minutes drive), for a minimum of 100 days after transplant or longer if there are complications. The participants must commit to having an adult caregiver with them during the first 100 days after the transplant

You may not qualify if:

• All participants
• Recipients who are receiving any investigational agent except virus specific T cells (VST)
• Active non-hematologic malignancies
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in study.
• Participants with the following cardiac conditions: symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (except atrial fibrillation if cleared by cardiology consultation)
• Participants without access to medical care at home.
• Positive serum or urine beta-human chorionic gonadotropin (beta-hCG) test at screening
• Uncontrolled intercurrent illness evaluated by history, physical exam, and laboratory studies or situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia; Lymphoma

Interventions

Cyclophosphamide; Busulfan; fludarabine; Whole-Body Irradiation; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Lea C Cunningham, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashley E Carpenter

CONTACT

(240) 550-0492; carpentera@mail.nih.gov

Lea C Cunningham, M.D.

CONTACT

(301) 642-1633; lea.cunningham@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: April 13, 2026
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): June 1, 2036
• Last Updated: April 16, 2026

Record last verified: 2026-04-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.

Locations

US (1)