ALLO-BAT: Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Hematopoietic stem cell transplant (HCT) Standard of care hematopoietic stem cell transplant with a matched donor. |
Biological: Hematopoietic stem cell transplant
Intravenous infusion of hematopoietic stem cells from a donor.
|
| Best available non-transplant therapies (BAT) Standard of care treatment with a janus kinase (JAK) inhibitor drug called ruxolitinib or treatment with an antimetabolite drug called hydroxyurea. |
Drug: Ruxolitinib
Ruxolitinib is type of drug called a janus kinase (JAK) inhibitor. Ruxolitinib is taken orally (by mouth).
Other Names:
Drug: Hydroxyurea
Hydroxyurea is a type of drug called an antimetabolite. Hydroxyurea is taken orally (by mouth).
|
Outcome Measures
Primary Outcome Measures
- Number of patients allocated to hematopoietic stem cell transplantation (HCT) [5 years]
- Number of patients allocated to best available non-transplant therapies (BAT) [5 years]
- Overall survival rate of patients who receive hematopoietic stem cell transplantation (HCT) [5 years]
Time from study allocation to death or last follow up.
- Overall survival rate of patients who receive best available non-transplant therapies (BAT) [5 years]
Time from study allocation to death or last follow up.
Secondary Outcome Measures
- Median change in Patient Global Impression of Change (PGIC) score [0 and 36 months]
Range from -3 to 3. Positive number equals increase in quality of life.
- Median change in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) [0 and 36 months]
Range from 0 to 10. Increase equals worsening of symptoms.
- Median change in FACT-BMT Questionnaire [0 and 36 months]
Range from 1 to 4. Increase equals increase in quality of life.
- Disease-free survival of patients who receive hematopoietic stem cell transplantation (HCT) [5 years]
Time from allocation to study arm to death/acute myeloid leukemia transformation or last follow up.
- Disease-free survival of patients who receive best available non-transplant therapies (BAT) [5 years]
Time from allocation to study arm to death/acute myeloid leukemia transformation or last follow up.
- Number of patients who receive hematopoietic stem cell transplantation (HCT) in remission (complete and partial) [3 years]
- Number of patients who receive best available non-transplant therapies (BAT) in remission (complete and partial) [3 years]
Eligibility Criteria
Criteria
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.
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Eastern Cooperative Oncology Group (ECOG) performance status 0-2
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Able to provide informed consent
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Adequate organ function
-
Donor search initiated or patient is agreeable to donor search
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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
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ECOG performance status 0-2
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Adequate organ function
-
Information on donor search and donor type available
Exclusion Criteria:
Recruitment Part:
-
Blasts in peripheral blood or bone marrow ≥10%
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For patients already on ruxolitinib at study entry, and meet the criteria of ruxolitinib failure
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Previous history of transformation to blast phase or acute myeloid leukemia
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Received allogeneic stem cell transplant for myeloproliferative neoplasm
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Presence of an active uncontrolled infection
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Myocardial infarction in the preceding 3 months
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Active hepatitis A, B or C
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Known human immunodeficiency virus (HIV) positive
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History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer
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Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.
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Pregnant or breastfeeding women
Study Arm Allocation:
-
Blasts in peripheral blood or bone marrow ≥10%
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Meet the criteria of ruxolitinib failure
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Presence of an active uncontrolled infection
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Myocardial infarction in the preceding 3 months
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Active hepatitis A, B or C
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Known HIV positive
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History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer
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Pregnant or breastfeeding women
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Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.
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Time between registration and allocation of study arm >24 weeks
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N4N2 |
| 2 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G2G3 |
| 3 | St. Paul's Hospital | Vancouver | British Columbia | Canada | V6E1M7 |
| 4 | Nova Scotia Health Authority | Halifax | Nova Scotia | Canada | B3H2Y9 |
| 5 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G2M9 |
Sponsors and Collaborators
- University Health Network, Toronto
Investigators
- Principal Investigator: Vikas Gupta, M.D., Princess Margaret Cancer Centre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19-6362
- ALLO-BAT