Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis

Myelofibrosis Clinical Trial

— ALLO-BAT  

Official title:

A Patient Preferences-Controlled Study of Allogeneic Hematopoietic Cell Transplantation Versus Best Available Non-Transplant Therapies in Patients With High-Risk Myelofibrosis (ALLO-BAT Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04217356
• Other study ID #: 19-6362
• Secondary ID: ALLO-BAT
• Status: Recruiting
• Start date: August 5, 2020
• Est. completion date: February 5, 2026

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: Vikas Gupta, M.D.
• Phone: 416-946-2885
• Email: vikas.gupta[@]uhn.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this research study is to see how effective hematopoietic stem cell transplantation (HCT) is compared to best available non-transplant therapies (BAT) in patients with high risk myelofibrosis. This will be done by asking participants to choose the treatment that they prefer to receive (HCT or BAT) and then comparing the outcomes of the participants in both treatment groups.

Description:

There is currently little information regarding which treatments are best for patients with myelofibrosis. On one hand, hematopoietic stem cell transplantation (HCT) is potentially curative treatment but is associated with significant risk of complications related to graft failure (the new donor cells does not grow properly after the transplant), side effects such as graft versus host disease (the patient's cells attack the new donor cells), and risk of infections. Non-transplant therapies such as ruxolitinib provide effective symptom control for few months to few years, but are not curative in nature. As such, this study will compare the effectiveness of HCT versus best available non-transplant therapies (BAT) in patients with high risk myelofibrosis.

This is an observational study, meaning that participants will be followed to assess the effects of their treatment, but no intervention (treatments) will be given as a part of this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: February 5, 2026
• Est. primary completion date: August 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Recruitment Part:

• Documented diagnosis of pre-fibrotic primary myelofibrosis (pre-fibrotic PMF), overt PMF, post-polycythemia MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF) confirmed by bone marrow biopsy

• Have been tested or have results available for phenotypic driver mutations (JAK2/CALR/MPL) and high molecular risk (HMR) mutations using a broad myeloid malignancies targeted gene panel.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Able to provide informed consent

• Adequate organ function

• Donor search initiated or patient is agreeable to donor search

• Meet the definition/criteria for high-risk myelofibrosis

Study Arm Allocation:

• Grade of fibrosis on bone marrow biopsy available according to World Health Organization (WHO) criteria

• Results available for phenotypic driver mutations (JAK2/CALR/MPL) and targeted sequencing results using a broad myeloid malignancy panel with a minimal requirement to include results on High molecular risk (HMR) mutations such as ASXL1/EZH2/IDH1/IDH2/SRSF2/U2AF1/TP53

• ECOG performance status 0-2

• Adequate organ function

• Information on donor search and donor type available

Exclusion Criteria:

Recruitment Part:

• Blasts in peripheral blood or bone marrow =10%

• For patients already on ruxolitinib at study entry, and meet the criteria of ruxolitinib failure

• Previous history of transformation to blast phase or acute myeloid leukemia

• Received allogeneic stem cell transplant for myeloproliferative neoplasm

• Presence of an active uncontrolled infection

• Myocardial infarction in the preceding 3 months

• Active hepatitis A, B or C

• Known human immunodeficiency virus (HIV) positive

• History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer

• Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.

• Pregnant or breastfeeding women

Study Arm Allocation:

• Blasts in peripheral blood or bone marrow =10%

• Meet the criteria of ruxolitinib failure

• Presence of an active uncontrolled infection

• Myocardial infarction in the preceding 3 months

• Active hepatitis A, B or C

• Known HIV positive

• History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer

• Pregnant or breastfeeding women

• Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.

• Time between registration and allocation of study arm >24 weeks

Related Conditions & MeSH terms

• Bone Marrow Cancer
• Bone Marrow Neoplasms
• High-Risk Cancer
• Myelofibrosis
• Primary Myelofibrosis

Intervention

Biological:
• Hematopoietic stem cell transplant
Intravenous infusion of hematopoietic stem cells from a donor.

Drug:
• Ruxolitinib
Ruxolitinib is type of drug called a janus kinase (JAK) inhibitor. Ruxolitinib is taken orally (by mouth).
• Hydroxyurea
Hydroxyurea is a type of drug called an antimetabolite. Hydroxyurea is taken orally (by mouth).

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients allocated to hematopoietic stem cell transplantation (HCT)		5 years
Primary	Number of patients allocated to best available non-transplant therapies (BAT)		5 years
Primary	Overall survival rate of patients who receive hematopoietic stem cell transplantation (HCT)	Time from study allocation to death or last follow up.	5 years
Primary	Overall survival rate of patients who receive best available non-transplant therapies (BAT)	Time from study allocation to death or last follow up.	5 years
Secondary	Median change in Patient Global Impression of Change (PGIC) score	Range from -3 to 3. Positive number equals increase in quality of life.	0 and 36 months
Secondary	Median change in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)	Range from 0 to 10. Increase equals worsening of symptoms.	0 and 36 months
Secondary	Median change in FACT-BMT Questionnaire	Range from 1 to 4. Increase equals increase in quality of life.	0 and 36 months
Secondary	Disease-free survival of patients who receive hematopoietic stem cell transplantation (HCT)	Time from allocation to study arm to death/acute myeloid leukemia transformation or last follow up.	5 years
Secondary	Disease-free survival of patients who receive best available non-transplant therapies (BAT)	Time from allocation to study arm to death/acute myeloid leukemia transformation or last follow up.	5 years
Secondary	Number of patients who receive hematopoietic stem cell transplantation (HCT) in remission (complete and partial)		3 years
Secondary	Number of patients who receive best available non-transplant therapies (BAT) in remission (complete and partial)		3 years