Acute Myeloid LeukemiaPhase 1NCT05720988
Tagraxofusp to Eradicate Measurable Residual Disease in Patients With Acute Myeloid Leukemia
A Phase 1 study testing Azacitidine and Tagraxofusp-erzs in people with Acute Myeloid Leukemia, run by Jonsson Comprehensive Cancer Center at 2 sites in United States.
Trial summary
This phase Ib/II trial tests the safety of tagraxofusp when given with or without azacitidine in patients with acute myeloid leukemia in remission with measurable residual disease who will undergo allogeneic hematopoietic cell transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Azacitidine and Tagraxofusp-erzs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Aug 2024to 3 Aug 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years
- AML in first or second remission, including:
- Complete remission (CR), defined as bone marrow blasts < 5%, absence of circulating blasts, absence of extramedullary disease, absolute neutrophil count (ANC) >= 1,000/uL, platelet count > 100,000/uL
- Complete remission with incomplete hematologic recovery (CRi), defined as all CR criteria except for residual neutropenia (ANC < 1,000/uL) or residual thrombocytopenia (platelet count < 100,000/uL)
- Morphologic leukemia-free state with adequate marrow recovery, defined as bone marrow blasts < 5%, ANC >= 500/uL, and platelet count >= 20,000/uL
- Minimal residual disease positive >= 0.01% based on MPFC
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- For participants in first remission, MRD positivity at any point from time of establishing first remission onward while still in first remission
- For participants in second remission, MRD positivity at any point from time of establishing second remission onward while still in second remission
- MRD must be repeated and remain positive if additional treatment is given prior to enrollment
- CD123 positivity on flow cytometry (partial, dim, or bright) from either:
- Conventional flow cytometry on marrow specimen from time of original diagnosis or first relapse
- High-sensitivity multiparametric flow cytometry on marrow specimen from time of MRD positivity
- Eastern Cooperative Oncology Group (ECOG) 0-2
- Serum albumin level >= 3.2 g/dL in the absence of receiving albumin infusion
- Serum total bilirubin =< 1.5 mg/dL, unless considered due to Gilbert's disease or medication effect
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase =< 2.5 times the upper limit of normal, unless considered due to medication effect (eg, azole therapy)
- Creatinine clearance >= 60 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR) and serum creatinine (Cr) =< 1.8 mg/dL
- Ability to give full informed consent
- Females of reproductive potential (postmenopausal for less than 24 consecutive months) must have a negative pregnancy test within 1 week of initiating treatment and may not be breastfeeding
Who cannot join
- MRD negativity < 0.01% at screening
- Intensive AML therapy within the past 14 days, or non-intensive targeted therapy within the past 7 days
- Cord blood as donor source
- Second malignancy that would be expected to limit survival within less than 2 years
- Cardiovascular disease that would result in high risk for toxicity, including:
- Uncontrolled or New York Heart Association (NYHA) class III or VI congestive heart failure
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- Recurrent or uncontrolled angina
- Unstable angina, myocardial infarction, or stroke in past 6 months
- Uncontrolled hypertension
- Arrhythmia not controlled by medication
- Left ventricular ejection fraction < 50%
- History of coronary stent placement that requires mandatory continuation of dual antiplatelet therapy
- Uncontrolled intercurrent illness that includes but is not limited to: uncontrolled infection, disseminated intravascular coagulation, psychiatric illness/compliance issues that would limit compliance with study protocol
- Any medical condition that in the opinion of the investigator places the participant at unacceptable risk for toxicity to investigational therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Habtemariam,Bruck
Los Angeles, California, 90095
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: Tagraxofusp-Based Therapy to Eradicate Measurable Residual Disease of Acute Myelogenous Leukemia Prior to Allogeneic Hematopoietic Cell Transplantation
This phase Ib/II trial tests the safety of tagraxofusp when given with or without azacitidine in patients with acute myeloid leukemia in remission with measurable residual disease who will undergo allogeneic hematopoietic cell transplant. Tagraxofusp is a recombinant protein consisting of IL-3 conjugated to a truncated diptheria toxin. The IL-3 attaches to the cancer cells and the toxic substance kills them. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Tagraxofusp and azacitidine may work better to kill cancer cells and eradicate measurable residual disease in patients with acute myeloid leukemia.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the safety and tolerability of tagraxofusp-erzs (tagraxofusp) with or without azacitidine in participants with acute myeloid leukemia (AML) in remission who are planned to undergo allogeneic hematopoietic cell transplantation (alloHCT).
SECONDARY OBJECTIVES:
- To estimate the rate of conversion from measurable residual disease (MRD) positive (>= 0.01% by multiparametric flow cytometry [MPFC]) pre-investigational therapy to MRD negative (=< 0.01% by MPFC) after 1 or 2 cycles of investigational therapy.
II. To estimate the rate of conversion from MRD positive (>= 0.01% by MPFC) pre-investigational therapy to MRD negative (=< 0.01% by MPFC) post-investigational therapy within 30 days prior to initiation of transplant conditioning regimen and at day +100 following alloHCT.
III. To evaluate if adverse effects of this investigational combination leads to delays in alloHCT.
IV. To evaluate if this investigational therapy results in liver toxicities after alloHCT such as sinusoidal obstruction syndrome.
- To evaluate relapse rate following alloHCT in participants who receive investigational therapy.
VI. To evaluate MRD progression following alloHCT in participants who receive investigational therapy.
VII. To evaluate 1-year survival following alloHCT in participants who receive investigational therapy.
EXPLORATORY OBJECTIVES:
- To estimate the rate of conversion from MRD positive to MRD negative by means of next generation sequencing.
II. To describe the level of CD123 expression on leukemia blasts in the bone marrow specimen at diagnosis and/or time of relapse and the association with achievement of MRD negativity post-investigational therapy.
III. To evaluate the number of days to full donor T-cell chimerism following alloHCT.
OUTLINE: This is a dose-escalation study of tagraxofusp-erzs . Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive tagraxofusp-erzs intravenously (IV) once daily (QD) over 15 minutes on days 1-5. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive azacitidine subcutaneously (SC) daily on days 1-5 and tagraxofusp-erzs IV QD over 15 minutes on days 8-12. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 months.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Azacitidine, Tagraxofusp-erzs
- 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.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given SC
Tagraxofusp-erzsBiological
Also called Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (tagraxofusp-erzs) | Active comparator | Patients receive tagraxofusp-erzs IV QD over 15 minutes on days 1-5. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Receives: Biological: Tagraxofusp-erzs |
| Cohort II (azacitidine, tagraxofusp-erzs) | Experimental | Patients receive azacitidine SC daily on days 1-5 and tagraxofusp-erzs IV QD over 15 minutes on days 8-12. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Azacitidine; Biological: Tagraxofusp-erzs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity
Grade >= 3 toxicity using Common Terminology Criteria for Adverse Events version 5.0 or severe persistent hematologic toxicity defined as absolute neutrophil count (ANC) < 500/uL OR platelet count < 10,000/uL in participants that have morphologic leukemia-free state (bone marrow blasts < 5%) are conditions for a dose limiting toxicity.
Measured: Up to 42 days
Secondary outcomes (7)
Measurable residual disease (MRD)
As measured by the University of Washington multiparametric flow cytometry (MPFC) assay with sensitivity of 0.01%
Measured: At the end of cycle 1 and cycle 2 (each cycle is 28 days).
MRD
As measured by the University of Washington MPFC assay with sensitivity of 0.01%.
Measured: Within 30 days prior to initiation of transplant conditioning regimen and at day 100 after transplant
Number of days between investigational regimen day 28 and initiation of transplant conditioning regimen
Measured: Between investigational regimen day 28 and initiation of transplant conditioning regimen, through study completion, an average of 1 year.
Rate of sinusoidal obstruction syndrome
Measured: up to 1 year following investigational therapy
Relapse
As defined by International Working Group criteria: the relapse rate and median duration of remission following allogeneic hematopoietic cell transplantation (HCT) will be reported along with an exact 95% confidence interval.
Measured: Up to 1 year
MRD progression
Defined by presence of leukemia blasts >0.01% at any time after achieving MRD negativity (<0.01%).
Measured: Up to 1 year
Overall survival
Kaplan-Meier methods will estimate the overall survival at 1 year following allogeneic (allo)HCT. This analysis will be performed using the FAS. The 1-year survival estimate will be reported along with a 95% confidence interval.
Measured: 1 year after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2023
- Study start3 Aug 2024 (estimated)
- Primary completion3 Aug 2025 (estimated)
- Study completion3 Aug 2026 (estimated)
Why it stopped: trial was not opened
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Stemline Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Caspian Oliai, MD, Principal investigator, UCLA / Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05720988
- Sponsor's protocol ID
- 21-001115
- Other IDs
- NCI-2021-12912
- Status last verified
- Jan 2023
- First submitted
- 11 Jan 2023
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tagraxofusp-Based Therapy to Eradicate Measurable Residual Disease of Acute Myelogenous Leukemia Prior to Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT05720988
- Acronym / sponsor ID
- 21-001115
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: trial was not opened
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Stemline Therapeutics, Inc.
- Study start
- 3 Aug 2024 (estimated)
- Primary completion
- 3 Aug 2025 (estimated)
- Study completion
- 3 Aug 2026 (estimated)
- First posted
- 9 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase Ib/II trial tests the safety of tagraxofusp when given with or without azacitidine in patients with acute myeloid leukemia in remission with measurable residual disease who will undergo allogeneic hematopoietic cell transplant. Tagraxofusp is a recombinant protein consisting of IL-3 conjugated to a truncated diptheria toxin. The IL-3 attaches to the cancer cells and the toxic substance kills them. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Tagraxofusp and azacitidine may work better to kill cancer cells and eradicate measurable residual disease in patients with acute myeloid leukemia.
Detailed description
PRIMARY OBJECTIVE:
- To determine the safety and tolerability of tagraxofusp-erzs (tagraxofusp) with or without azacitidine in participants with acute myeloid leukemia (AML) in remission who are planned to undergo allogeneic hematopoietic cell transplantation (alloHCT).
SECONDARY OBJECTIVES:
- To estimate the rate of conversion from measurable residual disease (MRD) positive (>= 0.01% by multiparametric flow cytometry [MPFC]) pre-investigational therapy to MRD negative (=< 0.01% by MPFC) after 1 or 2 cycles of investigational therapy.
II. To estimate the rate of conversion from MRD positive (>= 0.01% by MPFC) pre-investigational therapy to MRD negative (=< 0.01% by MPFC) post-investigational therapy within 30 days prior to initiation of transplant conditioning regimen and at day +100 following alloHCT.
III. To evaluate if adverse effects of this investigational combination leads to delays in alloHCT.
IV. To evaluate if this investigational therapy results in liver toxicities after alloHCT such as sinusoidal obstruction syndrome.
- To evaluate relapse rate following alloHCT in participants who receive investigational therapy.
VI. To evaluate MRD progression following alloHCT in participants who receive investigational therapy.
VII. To evaluate 1-year survival following alloHCT in participants who receive investigational therapy.
EXPLORATORY OBJECTIVES:
- To estimate the rate of conversion from MRD positive to MRD negative by means of next generation sequencing.
II. To describe the level of CD123 expression on leukemia blasts in the bone marrow specimen at diagnosis and/or time of relapse and the association with achievement of MRD negativity post-investigational therapy.
III. To evaluate the number of days to full donor T-cell chimerism following alloHCT.
OUTLINE: This is a dose-escalation study of tagraxofusp-erzs . Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive tagraxofusp-erzs intravenously (IV) once daily (QD) over 15 minutes on days 1-5. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive azacitidine subcutaneously (SC) daily on days 1-5 and tagraxofusp-erzs IV QD over 15 minutes on days 8-12. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort I (tagraxofusp-erzs) | Active comparator | Biological: Tagraxofusp-erzsPatients receive tagraxofusp-erzs IV QD over 15 minutes on days 1-5. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. |
| Cohort II (azacitidine, tagraxofusp-erzs) | Experimental | Drug: Azacitidine, Biological: Tagraxofusp-erzsPatients receive azacitidine SC daily on days 1-5 and tagraxofusp-erzs IV QD over 15 minutes on days 8-12. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age >= 18 years
- AML in first or second remission, including:
- Minimal residual disease positive >= 0.01% based on MPFC
- CD123 positivity on flow cytometry (partial, dim, or bright) from either:
- Eastern Cooperative Oncology Group (ECOG) 0-2
Key exclusion criteria (14 listed)
- MRD negativity < 0.01% at screening
- Intensive AML therapy within the past 14 days, or non-intensive targeted therapy within the past 7 days
- Cord blood as donor source
- Second malignancy that would be expected to limit survival within less than 2 years
- Cardiovascular disease that would result in high risk for toxicity, including:
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 |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven SC | Drug | Cohort II (azacitidine, tagraxofusp-erzs) |
| Tagraxofusp-erzsAlso: Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, ElzonrisGiven IV | Biological | Cohort I (tagraxofusp-erzs), Cohort II (azacitidine, tagraxofusp-erzs) |
Primary outcome
Dose-limiting toxicity
Time frame: Up to 42 days
Grade >= 3 toxicity using Common Terminology Criteria for Adverse Events version 5.0 or severe persistent hematologic toxicity defined as absolute neutrophil count (ANC) < 500/uL OR platelet count < 10,000/uL in participants that have morphologic leukemia-free state (bone marrow blasts < 5%) are conditions for a dose limiting toxicity.
7 secondary outcomes
Measurable residual disease (MRD)
Time frame: At the end of cycle 1 and cycle 2 (each cycle is 28 days).
MRD
Time frame: Within 30 days prior to initiation of transplant conditioning regimen and at day 100 after transplant
Number of days between investigational regimen day 28 and initiation of transplant conditioning regimen
Time frame: Between investigational regimen day 28 and initiation of transplant conditioning regimen, through study completion, an average of 1 year.
Rate of sinusoidal obstruction syndrome
Time frame: up to 1 year following investigational therapy
Relapse
Time frame: Up to 1 year
MRD progression
Time frame: Up to 1 year
Overall survival
Time frame: 1 year after transplant
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
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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.
Caspian Oliai, MD principal investigator
UCLA / Jonsson Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine and Tagraxofusp-erzs in people with Acute Myeloid Leukemia, run by Jonsson Comprehensive Cancer Center at 2 sites in United States.
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 19 inclusion and 14 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: withdrawn, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Dose-limiting toxicity (time frame: Up to 42 days). 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 8 Mar 2024.