Relapsed/Refractory LeukemiasPhase 1NCT05326516
A Study of Revumenib in Combination With Chemotherapy in Participants With R/R Acute Leukemia
A Phase 1 study testing Revumenib, Chemotherapy Regimen 1 and Chemotherapy Regimen 2 in people with Relapsed/Refractory Leukemias and Acute Lymphoblastic Leukemia, run by Syndax Pharmaceuticals at 11 sites in 2 countries.
Trial summary
The purpose of this study is to determine the safety and tolerability of revumenib when given in combination with 2 different chemotherapy regimens in participants with relapsed/refractory acute leukemias harboring KMT2A rearrangement, KMT2A amplification, NPM1c, or NUP98r. Read more about this study
- Who is it for?
- Ages 30 days and older
- Conditions the study is for
- Relapsed/Refractory Leukemias, Acute Lymphoblastic Leukemia, Acute Lymphocytic Leukemia
- What is being tested?
- Revumenib, Chemotherapy Regimen 1 and Chemotherapy Regimen 2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 9 Mar 2022to 29 Jul 2024
- 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 30 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants must have documented relapsed or refractory (R/R) AML, ALL, or acute leukemias of ambiguous lineage (ALAL) including MPAL and acute undifferentiated leukemia (AUL) harboring KMT2A rearrangement, KMT2A amplification, NPM1c, or NUP98r.
- White blood count must be <25,000/microliter prior to the first dose of revumenib. Participants may receive cytoreduction per protocol prior to beginning revumenib.
- Eastern Cooperative Oncology Group performance status score 0-2 (if aged ≥18 years); Karnofsky Performance Scale of ≥50 (if aged ≥16 years and <18 years); Lansky Performance Score of ≥50 (if aged <16 years).
- Adequate liver, kidney, and cardiac function
- Participant must be taking 1 of the following medications for antifungal prophylaxis: itraconazole, ketoconazole, posaconazole, or voriconazole.
- A female of childbearing potential must agree to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
- A male of childbearing potential must agree to use barrier contraception from the time of enrollment through 120 days following the last study drug dose.
Who cannot join
- Any unresolved ≥Grade 2 reversible toxicity from previous anticancer therapy except alopecia or Grade 2 neuropathy
- Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant participants must have discontinued all systemic immunosuppressive therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids.
- Concurrent malignancy in the previous 2 years, with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (for example, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in complete remission or no evidence of disease during this timeframe. For participants with therapy-related leukemia, primary disease must be in remission for 1-year following completion of therapy.
- If the participant is known to be human immunodeficiency virus (HIV)-positive, the participant must have undetectable HIV viral load within the previous 6 months.
- Hepatitis B
- Hepatitis C
Show all 19Show fewer
- Cardiac Disease:
- Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
- QTcF interval >450 milliseconds
- Any gastrointestinal (GI) issue of the upper GI tract that might affect oral drug absorption or ingestion (for example, gastric bypass, gastroparesis).
- Cirrhosis with a Child-Pugh score of B or C
- Down Syndrome
- Genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome.
- Participation in another therapeutic interventional clinical study within 28 days of starting revumenib.
- Radiation Therapy: within 60 days from prior total body irradiation, craniospinal radiation and/or ≥50% radiation of the pelvis, or within 14 days from local palliative radiation therapy (small port).
- Stem Cell Infusion or Donor Lymphocyte Infusion: within 60 days from hematopoietic stem cell transplantation and within 28 days from donor lymphocyte infusion without conditioning.
- Biologics (for example, monoclonal antibody therapy, bispecific antibodies, and antibody-drug conjugates): within 28 days or 5 half-lives, whichever is longer, since the completion of therapy with a biologic agent.
- Immunotherapy: within 42 days since tumor vaccines and checkpoint inhibitors, and within 21 days since receipt of chimeric antigen receptor therapy or other modified T-cell therapy.
- Hematopoietic Growth Factors: within 7 days since the completion of therapy with short-acting hematopoietic growth factors and within 14 days with long-acting growth factors.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
MD Anderson Cancer Center
Houston, Texas, 77030
Texas Children's Cancer and Hematology Center
Houston, Texas, 77030
Children's Mercy Hospital
Kansas City, Missouri, 64108
St. Jude Children's Research Hospital, Inc
Memphis, Tennessee, 38105
David H Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10021
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of California, San Francisco (UCSF) Benioff Children's Hospital
San Francisco, California, 94158
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: AUGMENT-102: A Phase 1, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability and Preliminary Anti-Leukemic Activity of SNDX-5613 in Combination With Chemotherapy in Patients With Relapsed/Refractory Leukemias Harboring Alterations in KMT2A/MLL, Nucleophosmin 1 (NPM1), and Nucleoporin 98 (NUP98) Genes
The purpose of this study is to determine the safety and tolerability of revumenib when given in combination with 2 different chemotherapy regimens in participants with relapsed/refractory acute leukemias harboring KMT2A rearrangement, KMT2A amplification, NPM1c, or NUP98r.
- Conditions
- Relapsed/Refractory Leukemias, Acute Lymphoblastic Leukemia, Acute Lymphocytic Leukemia, Mixed Phenotype Acute Leukemia, Acute Myeloid Leukemia, Acute Undifferentiated Leukemia
- Being tested
- Revumenib, Chemotherapy Regimen 1, Chemotherapy Regimen 2
- Keywords
- SNDX-5613, AUGMENT, KMT2A/MLL Gene Rearrangement, Nucleophosmin 1 Mutation, NPM1, Nucleoporin 98, NUP98, Menin, Revumenib
- Medical subject headings
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RevumenibDrug
Also called SNDX-5613
Participants will receive revumenib until meeting criteria for discontinuation.
Chemotherapy Regimen 1Drug
Participants will receive 2 treatment cycles of chemotherapy. During Cycle 1, participants will receive prednisone, vincristine, pegaspargase/calaspargase pegol-mknL, and daunorubicin. During Cycle 2, participants will receive etoposide and cyclophosphamide.
Chemotherapy Regimen 2Drug
Participants will receive 2 treatment cycles of chemotherapy. During Cycles 1 and 2, participants will receive fludarabine and cytarabine.
| Study group | Role | What they receive |
|---|---|---|
| Revumenib and Chemotherapy Regimen 1 | Experimental | Participants with acute lymphoblastic leukemia/mixed phenotype acute leukemia (ALL/MPAL) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 1. Receives: Drug: Revumenib; Drug: Chemotherapy Regimen 1 |
| Revumenib and Chemotherapy Regimen 2 | Experimental | Participants with ALL/MPAL or acute myeloid leukemia (AML) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 2. Receives: Drug: Revumenib; Drug: Chemotherapy Regimen 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities From Revumenib
Measured: Day 1 through up to 30 days after last dose of study intervention
Number of Participants With Treatment-emergent Adverse Events
Measured: Day 1 through up to 30 days after last dose of study intervention
Secondary outcomes (3)
Maximum Plasma Concentration (Cmax) of Revumenib
Measured: Predose through up to 6 hours postdose
Area Under The Plasma Concentration Versus Time Curve From Time 0 To t (AUC0-t) Of Revumenib
Measured: Predose through up to 6 hours postdose
Area Under The Concentration Versus Time Curve From Time 0 To 24 Hours (AUC0-24) Of Revumenib
Measured: Predose through up to 6 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2022
- Study start9 Mar 2022
- Primary completion29 Jul 2024
- Study completion29 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory LeukemiasStudies of the same condition, open and under way.
- 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
- Model description
- The study will use a Bayesian optimal interval (BOIN) design to evaluate the doses and determine the maximum tolerated dose.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nicole McNeer, MD, PhD, Study director, Syndax Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05326516
- Sponsor's protocol ID
- SNDX-5613-0702
- Status last verified
- Aug 2024
- First submitted
- 23 Mar 2022
- Last updated
- 13 Aug 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AUGMENT-102: A Phase 1, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability and Preliminary Anti-Leukemic Activity of SNDX-5613 in Combination With Chemotherapy in Patients With Relapsed/Refractory Leukemias Harboring Alterations in KMT2A/MLL, Nucleophosmin 1 (NPM1), and Nucleoporin 98 (NUP98) Genes
- ClinicalTrials.gov ID
- NCT05326516
- Acronym / sponsor ID
- SNDX-5613-0702
- Conditions
- Relapsed/Refractory Leukemias, Acute Lymphoblastic Leukemia, Acute Lymphocytic Leukemia, Mixed Phenotype Acute Leukemia, Acute Myeloid Leukemia, Acute Undifferentiated Leukemia
- Keywords
- SNDX-5613, AUGMENT, KMT2A/MLL Gene Rearrangement, Nucleophosmin 1 Mutation, NPM1, Nucleoporin 98, NUP98, Menin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Mar 2022 (actual)
- Primary completion
- 29 Jul 2024 (actual)
- Study completion
- 29 Jul 2024 (actual)
- First posted
- 13 Apr 2022 (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.
The purpose of this study is to determine the safety and tolerability of revumenib when given in combination with 2 different chemotherapy regimens in participants with relapsed/refractory acute leukemias harboring KMT2A rearrangement, KMT2A amplification, NPM1c, or NUP98r.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study will use a Bayesian optimal interval (BOIN) design to evaluate the doses and determine the maximum tolerated dose.
| Arm | Type | Receives |
|---|---|---|
| Revumenib and Chemotherapy Regimen 1 | Experimental | Drug: Revumenib, Drug: Chemotherapy Regimen 1Participants with acute lymphoblastic leukemia/mixed phenotype acute leukemia (ALL/MPAL) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 1. |
| Revumenib and Chemotherapy Regimen 2 | Experimental | Drug: Revumenib, Drug: Chemotherapy Regimen 2Participants with ALL/MPAL or acute myeloid leukemia (AML) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 2. |
Who may qualify
- Ages
- 30 days and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Participants must have documented relapsed or refractory (R/R) AML, ALL, or acute leukemias of ambiguous lineage (ALAL) including MPAL and acute undifferentiated leukemia (AUL) harboring KMT2A rearrangement, KMT2A amplification, NPM1c, or NUP98r.
- White blood count must be <25,000/microliter prior to the first dose of revumenib. Participants may receive cytoreduction per protocol prior to beginning revumenib.
- Eastern Cooperative Oncology Group performance status score 0-2 (if aged ≥18 years); Karnofsky Performance Scale of ≥50 (if aged ≥16 years and <18 years); Lansky Performance Score of ≥50 (if aged <16 years).
- Adequate liver, kidney, and cardiac function
- Participant must be taking 1 of the following medications for antifungal prophylaxis: itraconazole, ketoconazole, posaconazole, or voriconazole.
Key exclusion criteria (19 listed)
- Any unresolved ≥Grade 2 reversible toxicity from previous anticancer therapy except alopecia or Grade 2 neuropathy
- Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant participants must have discontinued all systemic immunosuppressive therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids.
- Concurrent malignancy in the previous 2 years, with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (for example, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in complete remission or no evidence of disease during this timeframe. For participants with therapy-related leukemia, primary disease must be in remission for 1-year following completion of therapy.
- If the participant is known to be human immunodeficiency virus (HIV)-positive, the participant must have undetectable HIV viral load within the previous 6 months.
- Hepatitis B
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 |
|---|---|---|
| RevumenibAlso: SNDX-5613Participants will receive revumenib until meeting criteria for discontinuation. | Drug | Revumenib and Chemotherapy Regimen 1, Revumenib and Chemotherapy Regimen 2 |
| Chemotherapy Regimen 1Participants will receive 2 treatment cycles of chemotherapy. During Cycle 1, participants will receive prednisone, vincristine, pegaspargase/calaspargase pegol-mknL, and daunorubicin. During Cycle 2, participants will receive etoposide and cyclophosphamide. | Drug | Revumenib and Chemotherapy Regimen 1 |
| Chemotherapy Regimen 2Participants will receive 2 treatment cycles of chemotherapy. During Cycles 1 and 2, participants will receive fludarabine and cytarabine. | Drug | Revumenib and Chemotherapy Regimen 2 |
Primary outcome
Number of Participants With Dose Limiting Toxicities From Revumenib
Time frame: Day 1 through up to 30 days after last dose of study intervention
Number of Participants With Treatment-emergent Adverse Events
Time frame: Day 1 through up to 30 days after last dose of study intervention
3 secondary outcomes
Maximum Plasma Concentration (Cmax) of Revumenib
Time frame: Predose through up to 6 hours postdose
Area Under The Plasma Concentration Versus Time Curve From Time 0 To t (AUC0-t) Of Revumenib
Time frame: Predose through up to 6 hours postdose
Area Under The Concentration Versus Time Curve From Time 0 To 24 Hours (AUC0-24) Of Revumenib
Time frame: Predose through up to 6 hours postdose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Individual participant dataSharing planned: No
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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.
Nicole McNeer, MD, PhD study director
Syndax Pharmaceuticals
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Revumenib, Chemotherapy Regimen 1 and Chemotherapy Regimen 2 in people with Relapsed/Refractory Leukemias and Acute Lymphoblastic Leukemia, run by Syndax Pharmaceuticals at 11 sites in 2 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 7 inclusion and 19 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: finished, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of Participants With Dose Limiting Toxicities From Revumenib (time frame: Day 1 through up to 30 days after last dose of study intervention). The study lists 2 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 13 Aug 2024.