Acute Myeloid LeukemiaPhase 1/2NCT05447663
A Study of Siremadlin Alone and in Combination With Donor Lymphocyte Infusion in Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplant
A Phase 1/2 study testing Siremadlin in people with Acute Myeloid Leukemia and Allogeneic Stem Cell Transplantation, run by Novartis Pharmaceuticals at 6 sites in 3 countries.
Trial summary
The purpose of this study was to confirm a safe dose and schedule as well as the preliminary efficacy of siremadlin alone, and in combination with donor lymphocyte infusion (DLI), in adult participants with Acute Myeloid Leukemia (AML) who were in remission following allogeneic stem cell transplantation (allo-SCT) but… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Myeloid Leukemia, Allogeneic Stem Cell Transplantation
- What is being tested?
- Siremadlin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 23 Feb 2023to 26 Oct 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with AML diagnosis, who underwent one allo-SCT to treat AML and are currently at ≥ Day 60 but no later than Day 120 (≤ Day 120) post allo-SCT.
- Pre-allo-SCT - Participants must have any of the following risk factors that put them at high risk for relapse:
- AML in first CR (CR1) prior to allo-SCT with one of the following:
- Adverse risk genetic abnormalities per 2017 ELN risk stratification. Patients with TP53 mutant AML at diagnosis are eligible if they meet eligibility criteria.
- Therapy-related AML (t-AML).
- Secondary AML (sAML) [AML secondary to antecedent myelodysplastic syndrome (MDS) or AML secondary to myeloproliferative neoplasm (MPN)].
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- AML in second or greater CR (≥CR2) prior to allo-SCT.
- Allo-SCT must have the following characteristics:
- Unmanipulated/T cell-replete bone marrow or peripheral blood stem cells as a graft source.
- Matched related (family) donor (MFD) or matched unrelated donor (MUD): Human Leukocyte Antigen (HLA) matching of donor and recipient should be at a minimum of 8/8 antigen or allele matched at HLA-A, -B, -C, -DRB1 loci.
- Any conditioning regimen intensity is permitted, the use of anti-thymocyte globulin (ATG) or alemtuzumab or post-transplant cyclophosphamide as a part of conditioning is allowed.
- Donor lymphocytes are collected, cryopreserved and available for infusion (DLI), or obtaining donor lymphocytes for DLI is feasible (applicable only for part 2)
- Post-allo-SCT, participants must have achieved CR or CRi with no current evidence of hematologic relapse
- Eastern Cooperative Oncology Group (ECOG ) performance status 0, 1 or 2.
- Laboratory test results indicating adequate liver and kidney function laboratory test results
- Evidence of adequate engraftment: Absolute Neutrophil Count (ANC) ≥ 1.0x109/L, Platelets (PLT) ≥ 75x109/L, Hemoglobin (Hgb) ≥ 8 g/dL (within 14 days prior to start of study treatment)
Who cannot join
- Prior exposure to MDM-inhibitor
- Active acute GvHD (aGvHD) of any grade (per Harris et al 2016) and/or active chronic GvHD (cGvHD ) of any grade (per NIH criteria (Jagasia et al 2015)) requiring systemic therapy at time of study treatment initiation
- Past history of grade III or IV aGvHD and/or past history of moderate or severe cGvHD. History of lower grades of GvHD is permitted if GvHD resolved to grade 0 for at least 4 weeks prior to start of study treatment.
- Recipient of allo-SCT from MUD with ≥1 antigen or allele mismatch at HLA-A, -B, -C, -DRB1 locus (HLA matching < 8/8 antigens)
- Recipient of allo-SCT from a haploidentical family donor; and recipients of cord blood transplant as a graft source
- Prior systemic AML-directed treatments given at any time after allo-SCT (including DLI)
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- Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting study, whichever is longer
- GI disorders that may prevent the intake and absorption of oral siremadlin (eg, diarrhea, uncontrolled nausea/vomiting, GI bleeding, etc).
- Any concurrent severe and/or active uncontrolled bacterial, viral or fungal infection requiring parenteral antibacterial, antiviral or antifungal therapy. Prophylactic antimicrobial use (oral or parenteral) is allowed.
- Participants who require treatment with moderate or strong CYP3A inducers within 14 days prior to starting study treatment, or are expected to receive moderate or strong CYP3A inducers during the entire study
- Cardiac or cardiac repolarization abnormality, that are clinically significant
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Germany2 sites
Novartis Investigative Site
Augsburg, 86179
Novartis Investigative Site
Freiburg im Breisgau, 79106
Italy2 sites
Novartis Investigative Site
Bergamo, BG, 24127
Novartis Investigative Site
Bologna, BO, 40138
Spain2 sites
Novartis Investigative Site
Seville, Andalusia, 41013
Novartis Investigative Site
Valencia, 46026
About this study
Official title: A Phase Ib/II, Open Label Study of Siremadlin Monotherapy and in Combination With Donor Lymphocyte Infusion as a Treatment for Patients With Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplantation Who Are in Complete Remission But at High Risk for Relapse.
The purpose of this study was to confirm a safe dose and schedule as well as the preliminary efficacy of siremadlin alone, and in combination with donor lymphocyte infusion (DLI), in adult participants with Acute Myeloid Leukemia (AML) who were in remission following allogeneic stem cell transplantation (allo-SCT) but were at high risk for relapse based on the presence of pre-transplant risk factors.
Read the detailed description
This is a Phase Ib/II, single arm, open label, multi-center study of siremadlin as monotherapy and in combination with DLI, in adult participants with AML.
The primary purpose of the study was to confirm the safe dose and schedule of siremadlin monotherapy and in combination with DLI. The study is also designed to assess the preliminary efficacy in preventing hematologic relapse.
The study was initially planned to enroll approximately 38 participants starting with a dose confirmation of siremadlin monotherapy (part 1) to determine the siremadlin recommended dose, followed by a treatment strategy of siremadlin/DLI (Part 2).
After enrolling 8 participants (at the starting dose 30 mg/day on days 1-5 of a 28-day treatment cycle) in part 1, Novartis took the decision to put the enrollment in permanent halt and terminate the siremadlin program. For that reason, the enrollment in part 2 will not be open. The Novartis decision was not driven by any safety concerns.
In part 1 approximately 12 participants were planned to be enrolled in 2 cohorts (starting dose 30 mg/day on days 1-5 of a 28-day treatment cycle, dose level +1 at 40 mg/day and dose level -1 at 20 mg/day) and participants were planned to be treated for a maximum of 24 cycles.
In part 2, participants were planned to follow a treatment strategy, which contains three consecutive phases for a maximum of 24 cycles in total:
- A priming phase with siremadlin monotherapy at the recommended dose determined in Part 1 (for at least 2 cycles). Participants who were not eligible for the combination phase of siremadlin/DLI could continue priming phase with siremadlin monotherapy.
- A combination phase of siremadlin in combination with DLI (siremadlin/DLI) for participants who were eligible to receive DLI (up to a total of 3 combination cycles).
- A maintenance phase with siremadlin monotherapy.
- Being tested
- Siremadlin
- Keywords
- Acute Myeloid Leukemia, Acute myeloid leukemia post allogeneic stem cell transplantation, AML, allogeneic stem cell transplantation, HDM201, siremadlin, donor lymphocyte infusion, DLI, MDM2, p53, allo-SCT
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SiremadlinDrug
Also called HDM201
Siremadlin was administered at a starting dose of 30 mg/day on days 1-5 of a 28-day treatment cycle (Part 1).
| Study group | Role | What they receive |
|---|---|---|
| Siremadlin (HDM201) | Experimental | Participants with AML post allogeneic stem cell transplantation (allo-SCT) received siremadlin monotherapy in part 1 and were to have received siremadlin monotherapy as well as in combination with donor lymphocyte infusion in part 2. Receives: Drug: Siremadlin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Dose Limiting Toxicities (DLTs) With Siremadlin Monotherapy in Part 1 (Dose Confirmation With Siremadlin Monotherapy)
To determine the dose and schedule of siremadlin monotherapy that are tolerable without unacceptable toxicities as defined by the incidence of DLT during the first cycle of treatment in part 1. 'A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed, by the Investigator, to be at least possibly related to study treatment (siremadlin monotherapy and/or siremadlin in combination with Donor lymphocyte infusion (DLI)), and as unrelated to disease, disease progression, inter-current illness, or concomitant medications, that occurs during the DLT observation period and meets severity criteria as per protocol.
Measured: from cycle 1 day 1 (C1D1) to end of Cycle 1 (cycle = 28days)
Time to Dose Limiting Toxicity (DLT) With Siremadlin in Combination With Donor Lymphocyte Infusion (DLI), in Part 2
To determine the dose and schedule of siremadlin in combination with DLI that are tolerable without unacceptable toxicities (siremadlin recommended dose for combination), defined as time from start of combination phase to first DLT observed during the entire combination phase.
Measured: From Day 1 of combination Cycle 1 to Day 42 of the last cycle of combination phase (up to 3 cycles of siremadlin/DLI combination). Cycle duration: 42 days
Percentage of Participants Who Are Alive and Maintained Complete Remission (CR) or Complete Response With Incomplete Hematological Recovery (CRi) With no Evidence of Hematologic Relapse (Part 2)
This involves evaluating the preliminary efficacy of siremadlin (as monotherapy, in priming and/or maintenance, with or without siremadlin in combination with DLI) on the prevention of hematologic relapse.
Measured: Over 6 months from start of study treatment strategy (part 2 - siremadlin/DLI treatment strategy)
Secondary outcomes (11)
Participants Who Are Alive and Maintained CR or CRi With no Evidence of Hematologic Relapse (Part 1 -Siremadlin Monotherapy at the Recommended Dose for Part 2 )
This involves evaluating the preliminary efficacy of siremadlin monotherapy at the recommended dose for part 2 on prevention of hematologic relapse
Measured: Over 6 months from start of siremadlin monotherapy (part 1)
Time From Start of Study Treatment to the Date of First Documented Hematologic Relapse or Death Due to Any Cause, Whichever Occurs First
Assessment of relapse free survival (RFS) in part 2
Measured: From start of study treatment to up to 36 months from last patient first treatment
Cumulative Incidence of AML Relapse at 1 Year and 2 Years After Start of Study Treatment
Cumulative incidence of Acute Myeloid Leukemia (AML) relapse at one year and 2 years after the start of study treatment in part 1 and 2. Cumulative incidence of relapse (CIR) is defined as the time from start of study treatment to the date of first documented hematologic relapse. CIR was to be analyzed in the FAS population who initiated priming phase at siremadlin recommended dose (RD) in Part 2 and participants at the RD in Part 1.
Measured: 1 year and 2 years after start of study treatment
Time From Start of Study Treatment to the Date of Death From Any Cause
Assessment of Overall survival (OS) in part 2
Measured: From start of study treatment to up to 36 months from last patient first treatment
Incidence of Graft Versus Host Disease (GvHD)
Incidence of grade III or IV acute GvHD, and moderate to severe chronic GvHD in part 1. Part 2 never started.
Measured: From start of study treatment up to approx. 8 months
Percentage of Participants With Permanent Study Treatment Discontinuation Due to GvHD or Other Adverse Events
Percentage of participants with permanent discontinuation of study treatment due to GvHD or other adverse events in part 1. As part 2 was not started, there were no participants to analyze in part 2.
Measured: From start of study treatment up to approx. 8 months
Time From Start of Study Treatment to the Date of First Documented Occurrence or Worsening of Treatment Emergent Grade III or IV Acute GvHD, or Chronic GvHD Requiring Initiation of Systemic Immunosuppressive Treatment
Assessment of GvHD-free/relapse-free survival (GRPF) in Part 1 and 2. According to the study protocol, time-to-event endpoints in Part 1 were planned to be analyzed using Kaplan-Meier method only for participants who received siremadlin at the recommended dose for Part 2.
Measured: From start of treatment up to approx. 8 months
Pharmacokinetic (PK) Characteristic AUC of Siremadlin
AUC is the area under the concentration vs. time curve in part 1 and was based on plasma concentration. Part 2 did not open for enrollment due to recruitment halt and so no data was analyzed.
AUClast: The AUC from time zero to the last quantifiable concentration point (Tlast) (mass x time x volume-1).
AUC0-t: The area under the concentration vs. time Curve (AUC) from time zero to specified time point.
Measured: AUC from time 0 to 8hr postdose, AUC0- 8hr (Cycle 1 Day 1, Cycle 1 Day 5) in part 1 [each cycle is 28 days for monotherapy]
PK Characteristic Cmax of Siremadlin
The maximum (peak) observed plasma drug concentration following drug administration (mass x volume^-1) in part 1. Part 2 did not open for enrollment due to recruitment halt and so no data was analyzed.
Measured: from 0 to 24 hrs post-dose (Cycle 1 Day 1), from 0 to 8 hr post-dose (Cycle 1 Day 5) in part 1 [each cycle is 28 days for monotherapy]
PK Characteristic Tmax of Siremadlin
The time to reach maximum (peak) plasma drug concentration after drug administration (time) in part 1. Part 2 did not open for enrollment due to recruitment halt and so no data was analyzed.
Measured: from 0 to 24 hrs post-dose (Cycle 1 Day 1), from 0 to 8 hr post-dose (Cycle 1 Day 5) in part 1 [each cycle is 28 days for monotherapy]
PK Characteristic Ctrough of Siremadlin
Concentration that is just prior to the beginning of, or at the end of a dosing interval; corresponding to the pre-dose concentration in part 1 and 2. Part 2 never started.
Measured: Cycle 1 Day 1, Cycle 1 Day 5 in part 1; [each cycle is 28 days]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2022
- Study start23 Feb 2023
- Primary completion26 Oct 2023
- Study completion26 Oct 2023
Why it stopped: Study has been stopped following the strategic decision from the Sponsor. Not based on any safety findings or safety concerns with siremadlin.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Study started out a phase l/ll study but because it was terminated, it never made it to phase ll.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05447663
- Sponsor's protocol ID
- CHDM201K12201
- Other IDs
- 2021-003596-34
- Status last verified
- May 2025
- First submitted
- 28 Jun 2022
- Last updated
- 16 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Open Label Study of Siremadlin Monotherapy and in Combination With Donor Lymphocyte Infusion as a Treatment for Patients With Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplantation Who Are in Complete Remission But at High Risk for Relapse.
- ClinicalTrials.gov ID
- NCT05447663
- Acronym / sponsor ID
- CHDM201K12201
- Keywords
- Acute Myeloid Leukemia, Acute myeloid leukemia post allogeneic stem cell transplantation, AML, allogeneic stem cell transplantation, HDM201, siremadlin, donor lymphocyte infusion, DLI
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study has been stopped following the strategic decision from the Sponsor. Not based on any safety findings or safety concerns with siremadlin.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Feb 2023 (actual)
- Primary completion
- 26 Oct 2023 (actual)
- Study completion
- 26 Oct 2023 (actual)
- First posted
- 7 Jul 2022 (actual)
- Results
- Posted 14 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to confirm a safe dose and schedule as well as the preliminary efficacy of siremadlin alone, and in combination with donor lymphocyte infusion (DLI), in adult participants with Acute Myeloid Leukemia (AML) who were in remission following allogeneic stem cell transplantation (allo-SCT) but were at high risk for relapse based on the presence of pre-transplant risk factors.
Detailed description
This is a Phase Ib/II, single arm, open label, multi-center study of siremadlin as monotherapy and in combination with DLI, in adult participants with AML.
The primary purpose of the study was to confirm the safe dose and schedule of siremadlin monotherapy and in combination with DLI. The study is also designed to assess the preliminary efficacy in preventing hematologic relapse.
The study was initially planned to enroll approximately 38 participants starting with a dose confirmation of siremadlin monotherapy (part 1) to determine the siremadlin recommended dose, followed by a treatment strategy of siremadlin/DLI (Part 2).
After enrolling 8 participants (at the starting dose 30 mg/day on days 1-5 of a 28-day treatment cycle) in part 1, Novartis took the decision to put the enrollment in permanent halt and terminate the siremadlin program. For that reason, the enrollment in part 2 will not be open. The Novartis decision was not driven by any safety concerns.
In part 1 approximately 12 participants were planned to be enrolled in 2 cohorts (starting dose 30 mg/day on days 1-5 of a 28-day treatment cycle, dose level +1 at 40 mg/day and dose level -1 at 20 mg/day) and participants were planned to be treated for a maximum of 24 cycles.
In part 2, participants were planned to follow a treatment strategy, which contains three consecutive phases for a maximum of 24 cycles in total:
- A priming phase with siremadlin monotherapy at the recommended dose determined in Part 1 (for at least 2 cycles). Participants who were not eligible for the combination phase of siremadlin/DLI could continue priming phase with siremadlin monotherapy.
- A combination phase of siremadlin in combination with DLI (siremadlin/DLI) for participants who were eligible to receive DLI (up to a total of 3 combination cycles).
- A maintenance phase with siremadlin monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Study started out a phase l/ll study but because it was terminated, it never made it to phase ll.
| Arm | Type | Receives |
|---|---|---|
| Siremadlin (HDM201) | Experimental | Drug: SiremadlinParticipants with AML post allogeneic stem cell transplantation (allo-SCT) received siremadlin monotherapy in part 1 and were to have received siremadlin monotherapy as well as in combination with donor lymphocyte infusion in part 2. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Participants with AML diagnosis, who underwent one allo-SCT to treat AML and are currently at ≥ Day 60 but no later than Day 120 (≤ Day 120) post allo-SCT.
- Pre-allo-SCT - Participants must have any of the following risk factors that put them at high risk for relapse:
- Adverse risk genetic abnormalities per 2017 ELN risk stratification. Patients with TP53 mutant AML at diagnosis are eligible if they meet eligibility criteria.
- Therapy-related AML (t-AML).
- Secondary AML (sAML) [AML secondary to antecedent myelodysplastic syndrome (MDS) or AML secondary to myeloproliferative neoplasm (MPN)].
Key exclusion criteria (11 listed)
- Prior exposure to MDM-inhibitor
- Active acute GvHD (aGvHD) of any grade (per Harris et al 2016) and/or active chronic GvHD (cGvHD ) of any grade (per NIH criteria (Jagasia et al 2015)) requiring systemic therapy at time of study treatment initiation
- Past history of grade III or IV aGvHD and/or past history of moderate or severe cGvHD. History of lower grades of GvHD is permitted if GvHD resolved to grade 0 for at least 4 weeks prior to start of study treatment.
- Recipient of allo-SCT from MUD with ≥1 antigen or allele mismatch at HLA-A, -B, -C, -DRB1 locus (HLA matching < 8/8 antigens)
- Recipient of allo-SCT from a haploidentical family donor; and recipients of cord blood transplant as a graft source
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SiremadlinAlso: HDM201Siremadlin was administered at a starting dose of 30 mg/day on days 1-5 of a 28-day treatment cycle (Part 1). | Drug | Siremadlin (HDM201) |
Primary outcome
Rate of Dose Limiting Toxicities (DLTs) With Siremadlin Monotherapy in Part 1 (Dose Confirmation With Siremadlin Monotherapy)
Time frame: from cycle 1 day 1 (C1D1) to end of Cycle 1 (cycle = 28days)
To determine the dose and schedule of siremadlin monotherapy that are tolerable without unacceptable toxicities as defined by the incidence of DLT during the first cycle of treatment in part 1. 'A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed, by the Investigator, to be at least possibly related to study treatment (siremadlin monotherapy and/or siremadlin in combination with Donor lymphocyte infusion (DLI)), and as unrelated to disease, disease progression, inter-current illness, or concomitant medications, that occurs during the DLT observation period and meets severity criteria as per protocol.
Time to Dose Limiting Toxicity (DLT) With Siremadlin in Combination With Donor Lymphocyte Infusion (DLI), in Part 2
Time frame: From Day 1 of combination Cycle 1 to Day 42 of the last cycle of combination phase (up to 3 cycles of siremadlin/DLI combination). Cycle duration: 42 days
To determine the dose and schedule of siremadlin in combination with DLI that are tolerable without unacceptable toxicities (siremadlin recommended dose for combination), defined as time from start of combination phase to first DLT observed during the entire combination phase.
Percentage of Participants Who Are Alive and Maintained Complete Remission (CR) or Complete Response With Incomplete Hematological Recovery (CRi) With no Evidence of Hematologic Relapse (Part 2)
Time frame: Over 6 months from start of study treatment strategy (part 2 - siremadlin/DLI treatment strategy)
This involves evaluating the preliminary efficacy of siremadlin (as monotherapy, in priming and/or maintenance, with or without siremadlin in combination with DLI) on the prevention of hematologic relapse.
11 secondary outcomes
Participants Who Are Alive and Maintained CR or CRi With no Evidence of Hematologic Relapse (Part 1 -Siremadlin Monotherapy at the Recommended Dose for Part 2 )
Time frame: Over 6 months from start of siremadlin monotherapy (part 1)
Time From Start of Study Treatment to the Date of First Documented Hematologic Relapse or Death Due to Any Cause, Whichever Occurs First
Time frame: From start of study treatment to up to 36 months from last patient first treatment
Cumulative Incidence of AML Relapse at 1 Year and 2 Years After Start of Study Treatment
Time frame: 1 year and 2 years after start of study treatment
Time From Start of Study Treatment to the Date of Death From Any Cause
Time frame: From start of study treatment to up to 36 months from last patient first treatment
Incidence of Graft Versus Host Disease (GvHD)
Time frame: From start of study treatment up to approx. 8 months
Percentage of Participants With Permanent Study Treatment Discontinuation Due to GvHD or Other Adverse Events
Time frame: From start of study treatment up to approx. 8 months
Time From Start of Study Treatment to the Date of First Documented Occurrence or Worsening of Treatment Emergent Grade III or IV Acute GvHD, or Chronic GvHD Requiring Initiation of Systemic Immunosuppressive Treatment
Time frame: From start of treatment up to approx. 8 months
Pharmacokinetic (PK) Characteristic AUC of Siremadlin
Time frame: AUC from time 0 to 8hr postdose, AUC0- 8hr (Cycle 1 Day 1, Cycle 1 Day 5) in part 1 [each cycle is 28 days for monotherapy]
PK Characteristic Cmax of Siremadlin
Time frame: from 0 to 24 hrs post-dose (Cycle 1 Day 1), from 0 to 8 hr post-dose (Cycle 1 Day 5) in part 1 [each cycle is 28 days for monotherapy]
PK Characteristic Tmax of Siremadlin
Time frame: from 0 to 24 hrs post-dose (Cycle 1 Day 1), from 0 to 8 hr post-dose (Cycle 1 Day 5) in part 1 [each cycle is 28 days for monotherapy]
PK Characteristic Ctrough of Siremadlin
Time frame: Cycle 1 Day 1, Cycle 1 Day 5 in part 1; [each cycle is 28 days]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Siremadlin in people with Acute Myeloid Leukemia and Allogeneic Stem Cell Transplantation, run by Novartis Pharmaceuticals at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Dose Limiting Toxicities (DLTs) With Siremadlin Monotherapy in Part 1 (Dose Confirmation With Siremadlin Monotherapy) (time frame: from cycle 1 day 1 (C1D1) to end of Cycle 1 (cycle = 28days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.