Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers

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

Interventions

DRUG

Cyclophosphamide

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.

DRUG

Busulfan

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).

DRUG

Fludarabine

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

RADIATION

Total Body Irradiation

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

BIOLOGICAL

Hematopoietic stem cells

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.

DRUG

Tacrolimus

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

DRUG

Mycophenolate Mofetil

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Lea C Cunningham, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-27

Primary Completion

2033-06-01

Completion

2036-06-01

Countries

• United States

Study Locations