Using high doses of ruxolitinib and stem cell transplant for myelofibrosis patients with enlarged spleens

High Dose Ruxolitinib and Allogeneic Stem Cell Transplantation in Myelofibrosis Patients With Splenomegaly

This study is testing if giving high doses of ruxolitinib and busulfan before a stem cell transplant can help people with myelofibrosis and enlarged spleens live longer and have better recovery after the transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: ruxolitinib
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06345495 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of administering high doses of ruxolitinib and busulfan prior to allogeneic stem cell transplantation in patients with myelofibrosis and splenomegaly. The primary objective is to compare the survival and engraftment rates of participants at 100 days post-transplant against historical data. Secondary objectives include assessing overall survival, progression-free survival, and various complications related to the transplant process. The study also explores immune reconstitution and cytokine profiles as exploratory objectives.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with primary or secondary myelofibrosis and clinically significant splenomegaly.

Not a fit: Patients without a matched donor or those with severe liver or kidney dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve transplant outcomes and reduce complications for patients with myelofibrosis.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being evaluated for the first time.

Eligibility criteria

Inclusion Criteria:

1. Participants 18 years to less than or equal to 75 years.
2. Able to provide written consent.
3. Primary or secondary Myelofibrosis (may have received Jak inhibitors including ruxolitinib)
4. Enlarged spleen by palpation or imaging. For the purpose of this study, splenomegaly is defined as any clinically palpable spleen or spleen larger than 12 cms on imaging.
5. Has a fully matched (8/8:HLA A, B, C, DRB1) related or matched unrelated donor.
6. Adequate renal function, including:

   a. Serum creatinine \</= 1.5 mg/dL or estimated Glomerular Filtration Rate (eGFR using the CKI-EPI equation) \>/= 40 ml/min/1.73 m2.
7. Adequate liver function, including:

   1. ALT/AST \</= 3 x ULN
   2. Direct bilirubin \</= 1mg/dL
   3. No history of liver cirrhosis. No ascites.
8. Female participants of childbearing potential must have negative results for a serum pregnancy test. Female participants must agree to not breastfeed during the study and for 3 months post-completion of the study therapy.
9. Subjects who are of childbearing potential, sexually active, and at risk of pregnancy must agree to use a highly effective method of contraception for the duration of the active treatment and at least 3 months post-completion of the study therapy. Highly effective methods of contraception include the following:

   1. Hormonal contraception (i.e., birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
   2. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study agent administration. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.

Exclusion Criteria:

1. Positive beta HCG in females of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
2. Ejection fraction \<40%
3. Corrected DLCO \< 50%
4. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

   1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
   2. Active hepatitis B virus (HBV), hepatitis C (HCV), HIV or TB infection or requiring treatment for the same.
   3. Thrombosis including MI, Stroke, PE, DVT in the past 6 months

Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Uday Popat, MD — M.D. Anderson Cancer Center
• Study coordinator: Uday Popat, MD

Conditions Splenomegaly; Myelofibrosis