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Filgrastim, Cladribine, Cytarabine, and Mitoxantrone With Sorafenib in Treating Patients With Newly-Diagnosed, Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Addition of Sorafenib to G-CSF, Cladribine, Cytarabine and Mitoxantrone (G-CLAM) in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD Status: A Phase 1/2 Study

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02728050
Enrollment
84
Registered
2016-04-05
Start date
2016-12-01
Completion date
2023-04-04
Last updated
2023-07-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome, Myeloproliferative Neoplasm

Brief summary

This phase I/II trial studies the side effects and best dose of filgrastim (granulocyte colony-stimulating factor \[G-CSF\]), cladribine, cytarabine, and mitoxantrone, when given together with sorafenib and to see how well they work in treating patients with newly-diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome (likely to be more aggressive). Drugs used in chemotherapy, such as cladribine, cytarabine, and mitoxantrone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Colony-stimulating factors, such as filgrastim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving filgrastim, cladribine, cytarabine, and mitoxantrone together with sorafenib may kill more cancer cells.

Detailed description

OUTLINE: This is a phase I, dose-escalation study of mitoxantrone and sorafenib followed by a phase II study. INDUCTION: Patients receive mitoxantrone intravenously (IV) over 60 minutes on days 1-3 and sorafenib orally (PO) twice daily (BID) on days 10-19 in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim subcutaneously (SC) once daily (QD) on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2 hours on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients achieving partial remission (including MRD positive \[pos\] CR, CR with incomplete platelet recovery \[CRp\], and CR with incomplete count recovery \[CRi\]) or persistent AML may receive up to 2 cycles of induction therapy per the discretion of the treating physician. POST-REMISSION: Patients receive sorafenib PO BID on days 8-27 or 3 days prior to next cycle of treatment, whichever occurs first. Patients also receive filgrastim subcutaneously SC QD on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2 hours on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients achieving MRDneg CR may receive up to 4 cycles of post-remission therapy. Patients achieving disease response (MRDpos CR, CRi/CRp, or persistent disease) may receive up to two induction cycles and 1 cycle of post-remission therapy with mitoxantrone omitted in cycle 3. If they then enter MRDneg CR, they can proceed with up to a total of 4 cycles of post-remission therapy. MAINTENANCE THERAPY: Patients achieving MRDneg CR may receive maintenance therapy of sorafenib PO BID for up to 1 year. After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Interventions

DRUGCladribine

Given IV

DRUGCytarabine

Given IV

BIOLOGICALFilgrastim

Given SC

OTHERLaboratory Biomarker Analysis

Correlative studies

OTHERQuality-of-Life Assessment

Ancillary studies

DRUGMitoxantrone

Given IV

DRUGSorafenib

Given PO

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Bayer
CollaboratorINDUSTRY
University of Washington
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No

Inclusion criteria

* Age 18-60 years, inclusive * Newly diagnosed disease with either a diagnosis of high-risk MDS (\>= 10% blasts in marrow or blood), high-risk myeloproliferative neoplasm (MPN; \>= 10% blasts in blood or bone marrow), or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification. Patients with biphenotypic AML are eligible; such high-risk MDS or MPN have natural history much closer to AML than to lower risk MDS or MPN and have responded similarly to AML-type therapy. * Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution by appropriate clinical staff. Flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines. * Treatment-related mortality (TRM) score =\< 13.1 as calculated with simplified model * The use of hydroxyurea prior to study registration is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood cell (WBC) \> 100,000/uL, or acute symptoms can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m\^2/dose) prior to study day 0 enrollment * Bilirubin =\< 2 times institutional upper limit of normal unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 10 days prior to study day 0) * Serum creatinine =\< 2.0 mg/dL (assessed within 10 days prior to study day 0) * Left ventricular ejection fraction \>= 45%, assessed within 3 months prior to study day 0, e.g. by multi gated acquisition scan (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure * Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 3 months after the last dose of study drug * Provide written informed consent (or legal representative)

Exclusion criteria

* Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for CML-directed tyrosine kinase inhibitor treatment (excluding sorafenib) * Concomitant illness associated with a likely survival of \< 1 year * Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired \[e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)\]). Patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24-48 hours prior to study day 0, unless fever is thought to be secondary to the underlying hematologic disease. * Active or clinically significant (or symptomatic) cardiac disease, including active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin within the last 3 months, unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before study day 0 * Previous receipt of azacitidine, decitabine, anthracyclines, cytarabine, or other nucleoside analogues for treatment of AML or MPN/MDS other than as noted for cytarabine * Pregnancy or lactation * Concurrent treatment with any other investigational agent that has anti-leukemia activity or another drug with anti-AML-activity

Design outcomes

Primary

MeasureTime frameDescription
Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of MitoxantroneFirst 28 days of treatmentMTD/RP2D will be defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is \< 33% assuming at least 6 patients have been treated at this dose. DLTs were defined as: 1) grade ≥3 non-hematologic toxicity lasting \>48 hours leading to \>7-day delay of the next cycle; 2) grade ≥4 non-hematologic toxicity if no recovery to grade ≤2 in 14 days (both excluding febrile neutropenia/ infection); 3) Absolute neutrophil count \<500/ µL or platelet count \<50,000/µL for \>49 days after CLAGM+S without marrow evidence of AML. Doses were escalated up to dose level six if \<2/6 patients out of each cohort of 6 had a DLT (some cohorts were expanded to 12 patients while awaiting completion of DLT monitoring period). The dose level at which dose escalation was stopped was the recommended phase 2 dose (RP2D).
Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of SorafenibFirst 28 days of treatmentMTD/RP2D will be defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is \< 33% assuming at least 6 patients have been treated at this dose. DLTs were defined as: 1) grade ≥3 non-hematologic toxicity lasting \>48 hours leading to \>7-day delay of the next cycle; 2) grade ≥4 non-hematologic toxicity if no recovery to grade ≤2 in 14 days (both excluding febrile neutropenia/ infection); 3) Absolute neutrophil count \<500/ µL or platelet count \<50,000/µL for \>49 days after CLAGM+S without marrow evidence of AML. Doses were escalated up to dose level six if \<2/6 patients out of each cohort of 6 had a DLT (some cohorts were expanded to 12 patients while awaiting completion of DLT monitoring period). The dose level at which dose escalation was stopped was the recommended phase 2 dose (RP2D).
Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)56 days (2 cycles of induction chemotherapy)We will determine if the addition of sorafenib to CLAG-M improves the rate of MRDneg CR compared to our institution's historical control of CLAG-M alone in adults with newly-diagnosed AML/high-risk MDS.

Secondary

MeasureTime frameDescription
Event-free Survival (EFS)12 months12-month event free survival
Complete Remission (CR)Up to 5 yearsComplete remission (CR) is defined as bone marrow blasts \<5%; absence of circulating blasts; absence of extramedullary disease; ANC ≥1.0 x 10\^9/L; platelet count ≥100 x 10\^9/L. CR with incomplete hematologic recovery (CRi) is CR with ANC \<1.0 x10\^9/L or platelet count \<100 x 10\^9/L. Measurable residual disease (MRD) is assessed by multiparameter flow cytometry and PCR. Morphologic leukemia free state (MLFS) is bone marrow blasts \<5%; absence of circulating blasts; absence of extramedullary disease; no hematologic recovery. Resistant disease is defined as not not meeting the criteria for CR, CRi, MLFS.
Number of Participants With Adverse EventsUp to 5 yearsWill be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Relapse-free Survival (RFS)12 months12-month relapse free survival (RFS)
Overall Response Rate (ORR)Up to 5 yearsORR, defined as CR+CRi, rates of patients treated with CLAG-M with sorafenib.
Overall Survival (OS)12 months12-month overall survival

Countries

United States

Participant flow

Participants by arm

ArmCount
Phase 1, Dose Level 1
Sorafenib 200mg PO BID days 10-19 Mitoxantrone 10mg/m\^2 IV days 1-3 G-CSF SQ 5µcg/kg days 0-5 Cladribine IV 5mg/m\^2 days 1-5 Cytarabine IV 2g/m\^2 days 1-5
6
Phase 1, Dose Level 2
Sorafenib 200mg PO BID days 10-19 Mitoxantrone 12mg/m\^2 IV days 1-3 G-CSF SQ 5µcg/kg days 0-5 Cladribine IV 5mg/m\^2 days 1-5 Cytarabine IV 2g/m\^2 days 1-5
6
Phase 1, Dose Level 3
Sorafenib 200mg PO BID days 10-19 Mitoxantrone 15mg/m\^2 IV days 1-3 G-CSF SQ 5µcg/kg days 0-5 Cladribine IV 5mg/m\^2 days 1-5 Cytarabine IV 2g/m\^2 days 1-5
11
Phase 1, Dose Level 4
Sorafenib 200mg PO BID days 10-19 Mitoxantrone 18mg/m\^2 IV days 1-3 G-CSF SQ 5µcg/kg days 0-5 Cladribine IV 5mg/m\^2 days 1-5 Cytarabine IV 2g/m\^2 days 1-5
8
Phase 1, Dose Level 5
Sorafenib 400mg AM, 200mg PM PO days 10-19 Mitoxantrone 18mg/m\^2 IV days 1-3 G-CSF SQ 5µcg/kg days 0-5 Cladribine IV 5mg/m\^2 days 1-5 Cytarabine IV 2g/m\^2 days 1-5
9
Phase 1, Dose Level 6
Sorafenib 400mg PO BID days 10-19 Mitoxantrone 18mg/m\^2 IV days 1-3 G-CSF SQ 5µcg/kg days 0-5 Cladribine IV 5mg/m\^2 days 1-5 Cytarabine IV 2g/m\^2 days 1-5
7
Phase 2, Dose Level 6
Sorafenib 400mg PO BID days 10-19 Mitoxantrone 18mg/m\^2 IV days 1-3 G-CSF SQ 5µcg/kg days 0-5 Cladribine IV 5mg/m\^2 days 1-5 Cytarabine IV 2g/m\^2 days 1-5
37
Total84

Baseline characteristics

CharacteristicPhase 1, Dose Level 1Phase 1, Dose Level 2Phase 1, Dose Level 3Phase 1, Dose Level 4Phase 1, Dose Level 5Phase 1, Dose Level 6Phase 2, Dose Level 6Total
Age, Customized40.5 years49.5 years41 years49 years56 years48 years49 years48 years
Disease classification
AML
5 Participants4 Participants11 Participants6 Participants7 Participants7 Participants29 Participants69 Participants
Disease classification
CMML-2
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants3 Participants3 Participants
Disease classification
MDS
1 Participants2 Participants0 Participants2 Participants2 Participants0 Participants5 Participants12 Participants
ECOG Performance Status
0
2 Participants1 Participants0 Participants2 Participants2 Participants1 Participants2 Participants10 Participants
ECOG Performance Status
1
4 Participants5 Participants9 Participants5 Participants7 Participants6 Participants32 Participants68 Participants
ECOG Performance Status
2
0 Participants0 Participants1 Participants1 Participants0 Participants0 Participants3 Participants5 Participants
ECOG Performance Status
3
0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
ELN 2017 Risk Group
Adverse
4 Participants2 Participants5 Participants3 Participants3 Participants1 Participants14 Participants32 Participants
ELN 2017 Risk Group
Favorable
2 Participants2 Participants4 Participants0 Participants5 Participants2 Participants10 Participants25 Participants
ELN 2017 Risk Group
Intermediate
0 Participants2 Participants2 Participants5 Participants0 Participants4 Participants13 Participants26 Participants
ELN 2017 Risk Group
Unable to assess
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants1 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants6 Participants1 Participants1 Participants0 Participants0 Participants2 Participants11 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants0 Participants10 Participants7 Participants9 Participants7 Participants35 Participants73 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
FLT3 Mutations
FLT3-ITD mutation
0 Participants2 Participants2 Participants2 Participants2 Participants3 Participants10 Participants21 Participants
FLT3 Mutations
FLT3 mutation status unknown
1 Participants1 Participants0 Participants1 Participants1 Participants0 Participants1 Participants5 Participants
FLT3 Mutations
FLT3-TKD mutation
1 Participants0 Participants1 Participants0 Participants0 Participants2 Participants2 Participants6 Participants
FLT3 Mutations
No FLT3 mutations
4 Participants3 Participants8 Participants5 Participants6 Participants2 Participants24 Participants52 Participants
MRC Risk Category
Adverse
2 Participants1 Participants2 Participants2 Participants2 Participants0 Participants10 Participants19 Participants
MRC Risk Category
Favorable
0 Participants0 Participants1 Participants0 Participants0 Participants1 Participants3 Participants5 Participants
MRC Risk Category
Intermediate
4 Participants5 Participants8 Participants6 Participants7 Participants6 Participants24 Participants60 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants1 Participants2 Participants0 Participants0 Participants1 Participants0 Participants4 Participants
Race (NIH/OMB)
Asian
1 Participants2 Participants0 Participants0 Participants0 Participants1 Participants4 Participants8 Participants
Race (NIH/OMB)
Black or African American
1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants2 Participants3 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants1 Participants1 Participants0 Participants1 Participants0 Participants0 Participants3 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants1 Participants
Race (NIH/OMB)
White
4 Participants2 Participants8 Participants8 Participants8 Participants5 Participants30 Participants65 Participants
Secondary Disease
No secondary disease
6 Participants6 Participants10 Participants3 Participants9 Participants7 Participants30 Participants71 Participants
Secondary Disease
Secondary disease
0 Participants0 Participants1 Participants5 Participants0 Participants0 Participants7 Participants13 Participants
Sex: Female, Male
Female
1 Participants4 Participants6 Participants7 Participants4 Participants5 Participants11 Participants38 Participants
Sex: Female, Male
Male
5 Participants2 Participants5 Participants1 Participants5 Participants2 Participants26 Participants46 Participants
Treatment Related Mortality (TRM) Score1.15 units on a scale2.00 units on a scale2.72 units on a scale2.19 units on a scale1.57 units on a scale1.28 units on a scale2.21 units on a scale1.96 units on a scale

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
deaths
Total, all-cause mortality
2 / 62 / 62 / 114 / 83 / 90 / 710 / 37
other
Total, other adverse events
6 / 66 / 610 / 118 / 88 / 96 / 727 / 37
serious
Total, serious adverse events
2 / 62 / 64 / 114 / 84 / 95 / 722 / 37

Outcome results

Primary

Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Mitoxantrone

MTD/RP2D will be defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is \< 33% assuming at least 6 patients have been treated at this dose. DLTs were defined as: 1) grade ≥3 non-hematologic toxicity lasting \>48 hours leading to \>7-day delay of the next cycle; 2) grade ≥4 non-hematologic toxicity if no recovery to grade ≤2 in 14 days (both excluding febrile neutropenia/ infection); 3) Absolute neutrophil count \<500/ µL or platelet count \<50,000/µL for \>49 days after CLAGM+S without marrow evidence of AML. Doses were escalated up to dose level six if \<2/6 patients out of each cohort of 6 had a DLT (some cohorts were expanded to 12 patients while awaiting completion of DLT monitoring period). The dose level at which dose escalation was stopped was the recommended phase 2 dose (RP2D).

Time frame: First 28 days of treatment

ArmMeasureValue (NUMBER)
CLAGM+Sorafenib Phase 1Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Mitoxantrone18 mg/m^2
Primary

Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Sorafenib

MTD/RP2D will be defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is \< 33% assuming at least 6 patients have been treated at this dose. DLTs were defined as: 1) grade ≥3 non-hematologic toxicity lasting \>48 hours leading to \>7-day delay of the next cycle; 2) grade ≥4 non-hematologic toxicity if no recovery to grade ≤2 in 14 days (both excluding febrile neutropenia/ infection); 3) Absolute neutrophil count \<500/ µL or platelet count \<50,000/µL for \>49 days after CLAGM+S without marrow evidence of AML. Doses were escalated up to dose level six if \<2/6 patients out of each cohort of 6 had a DLT (some cohorts were expanded to 12 patients while awaiting completion of DLT monitoring period). The dose level at which dose escalation was stopped was the recommended phase 2 dose (RP2D).

Time frame: First 28 days of treatment

ArmMeasureValue (NUMBER)
CLAGM+Sorafenib Phase 1Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Sorafenib400 mg BID
Primary

Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)

We will determine if the addition of sorafenib to CLAG-M improves the rate of MRDneg CR compared to our institution's historical control of CLAG-M alone in adults with newly-diagnosed AML/high-risk MDS.

Time frame: 56 days (2 cycles of induction chemotherapy)

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
CLAGM+Sorafenib Phase 1Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)3 Participants
Phase 1, Dose Level 2Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)6 Participants
Phase 1, Dose Level 3Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)8 Participants
Phase 1, Dose Level 4Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)4 Participants
Phase 1, Dose Level 5Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)9 Participants
Phase 1, Dose Level 6Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)7 Participants
Phase 2, Dose Level 6Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)31 Participants
Comparison: Participants on study receiving CLAGM-S were compared to a historical cohort of newly diagnosed AML/high-risk MDS patients treated with CLAG-M alone, matched for mitoxantrone dose, age, and TRM score.~Number of participants in historical cohort = 71. Number of participants in historical cohort who achieved MRD-negative CR = 55 (77.46%)p-value: 0.48Fisher Exact
Secondary

Complete Remission (CR)

Complete remission (CR) is defined as bone marrow blasts \<5%; absence of circulating blasts; absence of extramedullary disease; ANC ≥1.0 x 10\^9/L; platelet count ≥100 x 10\^9/L. CR with incomplete hematologic recovery (CRi) is CR with ANC \<1.0 x10\^9/L or platelet count \<100 x 10\^9/L. Measurable residual disease (MRD) is assessed by multiparameter flow cytometry and PCR. Morphologic leukemia free state (MLFS) is bone marrow blasts \<5%; absence of circulating blasts; absence of extramedullary disease; no hematologic recovery. Resistant disease is defined as not not meeting the criteria for CR, CRi, MLFS.

Time frame: Up to 5 years

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
CLAGM+Sorafenib Phase 1Complete Remission (CR)Resistant disease0 Participants
CLAGM+Sorafenib Phase 1Complete Remission (CR)CRi: MRD-negative1 Participants
CLAGM+Sorafenib Phase 1Complete Remission (CR)MLFS0 Participants
CLAGM+Sorafenib Phase 1Complete Remission (CR)Indeterminate0 Participants
CLAGM+Sorafenib Phase 1Complete Remission (CR)CR: MRD-negative3 Participants
CLAGM+Sorafenib Phase 1Complete Remission (CR)CRi: MRD-positive0 Participants
CLAGM+Sorafenib Phase 1Complete Remission (CR)CR: MRD-positive2 Participants
Phase 1, Dose Level 2Complete Remission (CR)CRi: MRD-negative0 Participants
Phase 1, Dose Level 2Complete Remission (CR)CR: MRD-negative6 Participants
Phase 1, Dose Level 2Complete Remission (CR)Resistant disease0 Participants
Phase 1, Dose Level 2Complete Remission (CR)CR: MRD-positive0 Participants
Phase 1, Dose Level 2Complete Remission (CR)MLFS0 Participants
Phase 1, Dose Level 2Complete Remission (CR)CRi: MRD-positive0 Participants
Phase 1, Dose Level 2Complete Remission (CR)Indeterminate0 Participants
Phase 1, Dose Level 3Complete Remission (CR)MLFS2 Participants
Phase 1, Dose Level 3Complete Remission (CR)CR: MRD-negative8 Participants
Phase 1, Dose Level 3Complete Remission (CR)CR: MRD-positive0 Participants
Phase 1, Dose Level 3Complete Remission (CR)Indeterminate0 Participants
Phase 1, Dose Level 3Complete Remission (CR)CRi: MRD-negative0 Participants
Phase 1, Dose Level 3Complete Remission (CR)Resistant disease1 Participants
Phase 1, Dose Level 3Complete Remission (CR)CRi: MRD-positive0 Participants
Phase 1, Dose Level 4Complete Remission (CR)MLFS0 Participants
Phase 1, Dose Level 4Complete Remission (CR)CRi: MRD-negative1 Participants
Phase 1, Dose Level 4Complete Remission (CR)CRi: MRD-positive0 Participants
Phase 1, Dose Level 4Complete Remission (CR)CR: MRD-negative4 Participants
Phase 1, Dose Level 4Complete Remission (CR)Resistant disease3 Participants
Phase 1, Dose Level 4Complete Remission (CR)CR: MRD-positive0 Participants
Phase 1, Dose Level 4Complete Remission (CR)Indeterminate0 Participants
Phase 1, Dose Level 5Complete Remission (CR)Resistant disease0 Participants
Phase 1, Dose Level 5Complete Remission (CR)CRi: MRD-negative0 Participants
Phase 1, Dose Level 5Complete Remission (CR)CR: MRD-negative9 Participants
Phase 1, Dose Level 5Complete Remission (CR)CR: MRD-positive0 Participants
Phase 1, Dose Level 5Complete Remission (CR)CRi: MRD-positive0 Participants
Phase 1, Dose Level 5Complete Remission (CR)MLFS0 Participants
Phase 1, Dose Level 5Complete Remission (CR)Indeterminate0 Participants
Phase 1, Dose Level 6Complete Remission (CR)MLFS0 Participants
Phase 1, Dose Level 6Complete Remission (CR)CRi: MRD-positive0 Participants
Phase 1, Dose Level 6Complete Remission (CR)Resistant disease0 Participants
Phase 1, Dose Level 6Complete Remission (CR)CR: MRD-positive0 Participants
Phase 1, Dose Level 6Complete Remission (CR)CR: MRD-negative7 Participants
Phase 1, Dose Level 6Complete Remission (CR)CRi: MRD-negative0 Participants
Phase 1, Dose Level 6Complete Remission (CR)Indeterminate0 Participants
Phase 2, Dose Level 6Complete Remission (CR)CR: MRD-negative31 Participants
Phase 2, Dose Level 6Complete Remission (CR)CRi: MRD-positive1 Participants
Phase 2, Dose Level 6Complete Remission (CR)Indeterminate1 Participants
Phase 2, Dose Level 6Complete Remission (CR)CRi: MRD-negative1 Participants
Phase 2, Dose Level 6Complete Remission (CR)CR: MRD-positive1 Participants
Phase 2, Dose Level 6Complete Remission (CR)MLFS0 Participants
Phase 2, Dose Level 6Complete Remission (CR)Resistant disease2 Participants
Secondary

Event-free Survival (EFS)

12-month event free survival

Time frame: 12 months

ArmMeasureValue (NUMBER)
CLAGM+Sorafenib Phase 1Event-free Survival (EFS)81 percentage of participants
Secondary

Number of Participants With Adverse Events

Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Time frame: Up to 5 years

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
CLAGM+Sorafenib Phase 1Number of Participants With Adverse Events6 Participants
Phase 1, Dose Level 2Number of Participants With Adverse Events6 Participants
Phase 1, Dose Level 3Number of Participants With Adverse Events11 Participants
Phase 1, Dose Level 4Number of Participants With Adverse Events8 Participants
Phase 1, Dose Level 5Number of Participants With Adverse Events9 Participants
Phase 1, Dose Level 6Number of Participants With Adverse Events7 Participants
Phase 2, Dose Level 6Number of Participants With Adverse Events32 Participants
Secondary

Overall Response Rate (ORR)

ORR, defined as CR+CRi, rates of patients treated with CLAG-M with sorafenib.

Time frame: Up to 5 years

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
CLAGM+Sorafenib Phase 1Overall Response Rate (ORR)6 Participants
Phase 1, Dose Level 2Overall Response Rate (ORR)6 Participants
Phase 1, Dose Level 3Overall Response Rate (ORR)8 Participants
Phase 1, Dose Level 4Overall Response Rate (ORR)5 Participants
Phase 1, Dose Level 5Overall Response Rate (ORR)9 Participants
Phase 1, Dose Level 6Overall Response Rate (ORR)7 Participants
Phase 2, Dose Level 6Overall Response Rate (ORR)34 Participants
Secondary

Overall Survival (OS)

12-month overall survival

Time frame: 12 months

ArmMeasureValue (NUMBER)
CLAGM+Sorafenib Phase 1Overall Survival (OS)86 percentage of participants
Secondary

Relapse-free Survival (RFS)

12-month relapse free survival (RFS)

Time frame: 12 months

ArmMeasureValue (NUMBER)
CLAGM+Sorafenib Phase 1Relapse-free Survival (RFS)82 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 11, 2026