Momelotinib in Combination With Hypomethylating Agent for Chronic Phase Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Chronic Neutrophilic Leukemia
- Conditions
- Chronic Myelomonocytic LeukemiaChronic Neutrophilic LeukemiaMyelodysplastic SyndromesMyeloproliferative Overlap Neoplasms
- Interventions
- Registration Number
- NCT07071155
- Brief Summary
This research is being done to evaluate effectiveness, safety, and tolerability of a study drug called momelotinib in participants with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) or chronic neutrophilic leukemia (CNL), in addition to standard treatment which usually includes a hypomethylating agent like azacitidine or decitabine. Treatment options for this diagnosis remain limited and investigators need better treatments to help control the disease, improve symptoms, and potentially help more patients become eligible for transplant.
Participants for this study will be asked to take some screening tests which will include routine physical examination, blood tests, and imaging scans to determine eligibility for the study. Those who continue to qualify for this study will begin treatment. The treatment on this study will include taking momelotinib by mouth for all patients. The first 10 patients may receive momelotinib (MMB) alone for 3 cycles before adding a standard treatment for MDS/MPN called azacitidine (HMA).
The participant may be asked to remain on the treatment for up to 24 months, depending upon how the participant is responding to the study treatment. After the study treatment is completed, the participant will have one additional clinic visit for evaluating overall health, physical examination and blood tests, that will be described later in detail.
The most common side effect that may be related to participation in this study can include (i) infections which can present as fever, chills, cough, breathing problems, diarrhea, vomiting, pain or burning with urination; or (ii) low blood platelet count which can result in bruising or bleeding for longer than usual if the participant hurts themself.
- Detailed Description
This is an open-label study of MMB-HMA in MDS/MPN and CNL that will enroll up to 18 patients. The investigators will randomize the first 10 patients (5 each) to receive MMB monotherapy for first 3 cycles with addition of HMA starting cycle 4 (Arm A) versus starting with HMA-MMB combination starting cycle 1 (Arm B). The reason to randomize is to see if the clinical outcomes and related data are comparable with both of these 2 approaches. The investigators will then have an interim analysis after the first 10 randomized patients. Depending on the outcome of this analysis, the next 8 patients (Arm C) will be treated according to Arm A, with MMB monotherapy, or according to Arm B with combination therapy. Excessive progression will be defined as (i) progression occurring in 3 or more patients at week 12 (≥60%) in Arm A; Arm B progression as progression at week 12 in 2 or fewer patients (≤40% patients); or (ii) if there are 2 or more patients who experience progression in Arm A than in Arm B. If no excessive progression is noted, patients in Arm C will be treated like Arm A. If criteria for excessive progression are met, the 8 patients in Arm C will be treated according to Arm B.
The primary objective of this study is to estimate the efficacy of using MMB alone and in combination with hypomethylating agents (MMB-HMA) like azacitidine or decitabine in up to 18 patients with MDS/MPN and CNL.
Key Eligibility Criteria:
1. Patients with a WHO diagnosis of chronic myelomonocytic leukemia (CMML), MDS/MPN-not otherwise specified (MDS/MPN-NOS), MDS/MPN with neutrophilia (MDS/MPN-N), CNL.
2. Age greater than or equal to 18 years
3. Blood counts with platelets greater than 25,000/microL, ANC greater than or equal to 0.75 x 10\^9/L (without transfusion or growth factor support)
4. Baseline splenomegaly with greater than or equal to 5 cm below costal margin or greater than or equal to 450 cm3 on imaging (ultrasound, CT or MRI)
Treatment Description:
All patients regardless of race or gender who fit the eligibility criteria will be considered for this study. MMB will be administered at a dose of 200 mg daily. Azacitidine will be administered at 75 mg/m2 for days 1-5 in a 28-day cycle and decitabine will be administered at 20mg/m2 for days 1-5 in a 28-day cycle.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A- Monotherapy (MMB) Momelotinib Once daily momelotinib monotherapy (200mg capsule/day) for first 3 28-day cycles with addition of hypomethylating agents (HMA) e.g. azacitidine or decitabine) starting cycle 4. Azacitidine will be administered at 75 mg/m2 for days 1-5 in a 28-day cycle and decitabine will be administered at 20mg/m2 for days 1-5 in a 28-day cycle. Arm B- Combination therapy (MMB-HMA) Decitabine Combination of once daily 200mg capsule momelotinib plus hypomethylating agents (HMA), e.g. azacitidine or decitabine) starting cycle 1. Azacitidine will be administered at 75 mg/m2 for days 1-5 in a 28-day cycle and decitabine will be administered at 20mg/m2 for days 1-5 in a 28-day cycle. Arm A- Monotherapy (MMB) Azacitidine Once daily momelotinib monotherapy (200mg capsule/day) for first 3 28-day cycles with addition of hypomethylating agents (HMA) e.g. azacitidine or decitabine) starting cycle 4. Azacitidine will be administered at 75 mg/m2 for days 1-5 in a 28-day cycle and decitabine will be administered at 20mg/m2 for days 1-5 in a 28-day cycle. Arm B- Combination therapy (MMB-HMA) Momelotinib Combination of once daily 200mg capsule momelotinib plus hypomethylating agents (HMA), e.g. azacitidine or decitabine) starting cycle 1. Azacitidine will be administered at 75 mg/m2 for days 1-5 in a 28-day cycle and decitabine will be administered at 20mg/m2 for days 1-5 in a 28-day cycle. Arm A- Monotherapy (MMB) Decitabine Once daily momelotinib monotherapy (200mg capsule/day) for first 3 28-day cycles with addition of hypomethylating agents (HMA) e.g. azacitidine or decitabine) starting cycle 4. Azacitidine will be administered at 75 mg/m2 for days 1-5 in a 28-day cycle and decitabine will be administered at 20mg/m2 for days 1-5 in a 28-day cycle. Arm B- Combination therapy (MMB-HMA) Azacitidine Combination of once daily 200mg capsule momelotinib plus hypomethylating agents (HMA), e.g. azacitidine or decitabine) starting cycle 1. Azacitidine will be administered at 75 mg/m2 for days 1-5 in a 28-day cycle and decitabine will be administered at 20mg/m2 for days 1-5 in a 28-day cycle.
- Primary Outcome Measures
Name Time Method Number of participants who achieve a complete response 24 weeks Efficacy determination - complete response: number of participants who achieve a complete response as defined by international consortium response criteria for MDS/MPN in adults
Number of participants who achieve a partial response 24 weeks Efficacy determination - partial response: number of participants who achieve a partial response as defined by international consortium response criteria for MDS/MPN in adults
Number of participants who achieve a clinical benefit 24 weeks Efficacy determination - clinical benefit: number of participants who achieve a clinical benefit per MDS/MPN IWG criteria4
- Secondary Outcome Measures
Name Time Method Number of participants who experience a grade 3 or higher adverse events or severe event 2 years Safety and tolerability evaluation: number of participants who experience a grade 3 or higher adverse event events or severe adverse events as defined by CTCAE v.5.0
Patient Global Impression of Change (PGIC) questionnaire 12 weeks Evaluate efficacy of momelotinib plus hypomethylating agents azacitidine or decitabine (MMB-HMA) on Patient Global Impression of Change (PGIC) questionnaire. A 7-point scale (1-7) rating of overall improvement. Patients rate their change as 1="very much improved," 2="much improved," 3="minimally improved," 4="no change," 5="minimally worse," 6="much worse," or 7="very much worse." Lower values represent a better outcome.
Number of Participants Who Achieve Erythroid Response 24 weeks Number of participants who achieve erythroid response at week 24 per international consortium criteria
Proportion of Participants Who Achieve Spleen Size Reduction 12 weeks Determine the proportion of participants who achieve a spleen volume reduction of ≥ 35% from baseline at week 12
Patient Global Impression of Change (PGIC) 24 weeks Evaluate efficacy of momelotinib plus hypomethylating agents azacitidine or decitabine (MMB-HMA) on Patient Global Impression of Change (PGIC) questionnaire. A 7-point scale (1-7) rating of overall improvement. Patients rate their change as 1="very much improved," 2="much improved," 3="minimally improved," 4="no change," 5="minimally worse," 6="much worse," or 7="very much worse." Lower values represent a better outcome.
Proportion of participants Who Achieve Spleen Size Reduction 24 weeks Determine the proportion of participants who achieve a spleen volume reduction of ≥ 35% from baseline at week 24
Trough concentrations of MMB as single agent and in combination with HMA 24 weeks Evaluate trough concentrations at week 24 in Arm A and B
Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) 24 weeks Evaluate efficacy of momelotinib plus hypomethylating agents azacitidine or decitabine (MMB-HMA) on MPN-SAF TSS questionnaire. Score range 0-100, higher score worse symptoms.