Study of Select Combinations in Adults With Myelofibrosis

A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Combinations in Adult Patients With Myelofibrosis

ClinicalTrials.gov Identifier: NCT04283526

Novartis Reference Number: CMBG453D12101

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is to investigate the safety, pharmacokinetics (PK) and preliminary efficacy of both the combination of MBG453 and NIS793 with or without decitabine or spartalizumab as well as single agent MBG453 and/or NIS793 single agent in myelofibrosis (MF) subjects post treatment with a Janus Kinase (JAK) inhibitor.

In this study, combination therapies with novel agents including immune therapy will focus on determining the promising combinations that provide acceptable safety and efficacy independent of JAK inhibitors. Immune therapy combinations, such as MBG453 in combination with NIS793, might offer the potential to target MF across genetic heterogeneity.

The primary objective of this study is to characterize the safety, tolerability and recomended dose for each treatment combination (MBG453 + NIS793, MBG453 + NIS793 + decitabine, and MBG453 + NIS793 + spartalizumab)

Condition 
Primary Myelofibrosis
Myelofibrosis
PMF
Post-Essential Thrombocythemia Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Phase 
Phase 1
Overall status 
Not yet recruiting
Enrollment count 
195 participants
Start date 
Sep 15, 2020
Completion date 
Feb 26, 2024
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
MBG453
Intravenous. 600mg. Every first day of a 21-day cycle, or on days 8 and 29 of a 42-day cycle (when in combination with Decitabine).
Drug
NIS793
Intravenous. 2100mg. Every first day of a 21-day cycle, or on days 8 and 29 of a 42-day cycle (when in combination with Decitabine).
Drug
Spartalizumab
Intravenous. 300mg. Every first day of a 21-day cycle
Drug
Decitabine
Intravenous. Starting dose: 5mg/m2 (dose cap at 20mg/m2). On days 1, 2 and 3 of a 42-day cycle

Eligibility Criteria

Key inclusion criteria:

Signed informed consent must be obtained prior to participation in the study.
Male or female subjects must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
Subjects have a diagnosis of PMF as defined by the WHO criteria, or diagnosis of PET-MF or PPV-MF as defined by the IWG-MRT criteria (International Working Group for Myelofibrosis Research and Treatment).

Subjects must have been treated with a JAK inhibitor for ≥3 months with inadequate efficacy response defined as <10% spleen volume reduction by MRI or <30% decrease from baseline in spleen length by physical examination or regrowth to these parameters following an initial response.

And/or

Treatment for ≥28 days complicated by either:

Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months); or
Grade ≥3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while on treatment with JAK inhibitor.
Palpable spleen of at least 5 cm from the LCM to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline (an MRI/CT scan up to 8 weeks prior to first dose of study treatment can be accepted).
Absolute neutrophil count (ANC) ≥ 1000/μL.
Dose evaluation / Dose escalataion: Platelet count ≥ 75,000/μL without transfusion support Dose expansion: Platelet count ≥ 50,000/μL without transfusion support.

Key exclusion criteria:

Subjects with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), or peripheral blasts ≥ 10 %, or AML transfromed from previous MPN.
Subjects having received JAK inhibitors, systemic antineoplastic therapy (including unconjugated therapeutic antibodies, toxin immunoconjugates, and alpha-interferon) or any experimental therapy within 14 days or five half-lives, whichever is shorter, before the first dose of study treatment.
Prior autologous or allogeneic stem cell transplant at any time.
Candidate for allogenic hematopoietic stem cell transplantation at the time of enrolment.
Splenic irradiation within 6 months prior to the first dose of study treatment.
Prior splenectomy.

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]