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Acute Myeloid LeukemiaPhase 1/2SALMANCT05580861

Sulfasalazine in AML Treated by Intensive Chemotherapy: Elderly Patients-first Line Treatment

A Phase 1/2 study testing Sulfasalazine in people with Acute Myeloid Leukemia, run by Assistance Publique - Hôpitaux de Paris at 13 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Acute myeloid leukemia (AML) is a heterogeneous clonal myeloid neoplasm where abnormal proliferation and impaired differentiation of hematopoietic stem and myeloid progenitor cells impedes normal hematopoiesis. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Sulfasalazine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
13 sitesFrance
Study dates
17 May 2023to Dec 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged 60 years or older
  • With newly diagnosed acute myeloid leukemia (AML) (short course treatment with hydroxyurea and or steroids is acceptable). Patients with AML secondary to an antecedent Myelodysplastic Syndromes (MDS) or Myeloproliferative Neoplasms (MPN) are eligible, as those with therapy-related AML.
  • Eligible for intensive chemotherapy in the investigator's opinion
  • Leukaemia-associated immunophenotypes (LAIP) detected at screening allowing flow cytometry (FCM)-based Minimal Residual Disease monitoring (Phase II only).
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Aspartate transaminase (AST) and Alanine transaminanse (ALT) ≤ 3.0 times upper the limit of normal (ULN) and total and direct serum bilirubin ≤ 1.5 x ULN unless considered due to leukemia Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the MDRD equation
  • Written informed consent obtained prior to any screening procedures
  • Eligible for National Health Insurance in France

Who cannot join

  • Myeloid Sarcoma with < 20% bone marrow blasts
  • Patient who has received a vaccine injection with live-attenuated virus in the last three weeks
  • Proven central nervous system leukemic involvement
  • Favorable risk cytogenetics: t(15;17), t(8;21), inv(16) or t(16;16) or presence of PML-RARA, RUNX1-RUNX1T1 or CBFB-MYH11 fusion transcript.
  • Presence of FLT3-ITD or TKD mandating treatment with midostaurin.
  • Concurrent therapy with any cytotoxic drug within 3 weeks before the first study dose. Only hydroxyurea for the control of blood counts is permitted.
Show all 34Show fewer
  • Patients planned to received CPX-351 for myelodysplasia-related changes or therapy-related AML.
  • Previous treatment with sulfasalazine in the last 5 years or ongoing treatment with sulfasalazine or 5-aminosalicylic acid (5-ASA) for ulcerative colitis or inflammatory rheumatisms.
  • History of allergy SSZ, one of its metabolites (5-aminosalicylic acid, 5-ASA) or mesalazine, other sulfonylarylamines sulfonamides or salicylates, or sulfasalazine excipients History of allergic reaction to idarubicin or idarubicin excipients
  • History of allergic reaction to cytarabine or cytarabine excipients
  • Known glucose 6-phosphate dehydrogenase deficiency.
  • Known acute intermittent porphyria or porphyria variegata.
  • Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate treatment).
  • Other uncontrolled or active malignant disease within prior 12 months (excluding myelodysplastic syndrome; cutaneous basal cell carcinoma, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised).
  • Known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
  • Clinically active hepatitis B or hepatitis C infection.
  • Inability to swallow. Known malabsorption syndrome or other condition that may significantly impair absorption of oral study medications.
  • Participation in another therapeutic interventional clinical study within 30 days of enrolment.
  • Administration of any therapy considered investigational (i.e., used for non-approved indications(s) or in the context of a research investigation) within 5 drug half-lives (whichever is longer) prior to the first dose of study drug.
  • Previous treatment by anthracyclines
  • Any contraindication to use anthracyclines including uncontrolled coronary disease, severe renal failure, severe hepatic failure, recent myocardial infarction, symptomatic congestive heart failure, severe cardiomyopathy, significant arrhythmia as estimated by the investigator or left-ventricule ejection fraction (LVEF) <53% as assessed by echocardiography or Multigated Acquisition Scan (MUGA), anterior treatment by idarubicin and/or anthracyclines and anthracènediones beyond the maximum cumulative dose.
  • Any contraindication to use cytarabine including degenerative and toxic encephalopathy.
  • Any condition requiring treatment with digoxin.
  • Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study.
  • Females who are pregnant or breastfeeding.
  • In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use a highly effective contraceptive method for the entire treatment period and for at least 6 months after completion of protocol treatment.
  • Highly effective contraception methods include: combined (estrogen and progestogen containing) hormonal methods associated with inhibition of ovulation, intra-uterine device; surgical sterilization (including bilateral tubal occlusion, partner's vasectomy) or sexual abstinence if this is the preferred and usual lifestyle of the patient.
  • Male patients must not freeze or donate sperm starting at screening and throughout the treatment period and 3 months after the administration of the final dose of study medication.
  • In a heterosexually active woman of childbearing potential, unwillingness or inability to use a highly effective contraceptive method (as described above) for the entire treatment period and for at least 6 months after the administration of the final dose of study medication.
  • Women are not regarded as of childbearing potential if they are post-menopausal (at least 2 years without menses) or are surgically sterile (at least 1 month before enrollment).
  • Female patients must not donate or retrieve, for their own use, ova from the time of screening and throughout the treatment period, and for 12 weeks after the administration of the final dose of study medication.
  • Female patients must agree not to breastfeed from the time of screening and throughout the protocol period, and for (5 half-lives) days after the administration of the final dose of study medication.
  • Adults subjects to a legal protection order or unable to give their consent
  • Persons deprived of their freedom by judicial or administrative decision, person hospitalized without their consent by virtues of French Public Health Code articles L 3212-1 and L3213-1 and who are not subject to the provisions of article L 1121-8.

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Raphaël Itzykson, Pr contact

1 42 49 96 43 ext. +33

raphael.itzykson@aphp.fr

Jérôme Lambert, Pr contact

142499742 ext. +33

jerome.lambert@u-paris.fr

13 sites in 1 country

France13 sites, 13 recruiting

  • CHU Amiens

    Amiens

    Delphine Lebon, Dr, lebon.delphine@chu-amiens.fr

    Not yet recruiting

  • Hôpital Avicenne

    Bobigny

    Thorsten Braun, Pr, thorsten.braun@aphp.fr

    Not yet recruiting

  • CHU Caen

    Caen

    Sylvain Chantepie, Dr, Chantepie-s@chu-caen.fr

    Not yet recruiting

  • CHU Henri Mondor

    Créteil

    Mathieu Leclerc, Dr, mathieu.leclerc@aphp.fr

    Recruiting

  • Centre Hospitalier Lyon Sud, Lyon

    Lyon

    Mael Heiblig, Dr, mael.heiblig@chu-lyon.fr

    Recruiting

  • Hôpital de la Conception, AP-HM

    Marseille

    Geoffroy Venton, Dr, geoffroy.venton@ap-hm.fr

    Not yet recruiting

  • CHU Nice

    Nice

    Thomas Cluzeau, Pr, cluzeau.t@chu-nice.fr

    Recruiting

  • AP-HP Hôpital Saint Louis

    Paris, 75010

    Rapahël Irzykson, MD PhD

    Recruiting

  • AP-HP Hôpital Cochin

    Paris, 75014

    Justine Decroocq, MD

    Recruiting

  • Centre Henri Becquerel

    Rouen

    Emilie Lemasle, Dr, Emilie.lemasle@chb.unicancer.fr

    Not yet recruiting

  • CHU Tours

    Tours

    Emmanuel Gyan, Pr, e.gyan@chu-tours.fr

    Recruiting

  • CH Mignot

    Versailles

    Juliette Lambert, MD PhD

    Recruiting

  • Gustave Roussy

    Villejuif

    Stephane de Botton, Dr, Stephane.DEBOTTON@gustaveroussy.fr

    Not yet recruiting

Other trials in France

About this study

Official title: Phase I/II Clinical Trial Assessing the Combination of Sulfasalazine With Standard of Care Induction Therapy in Newly Diagnosed Acute Myeloid Leukemias (AML) Patients 60 Years or Older- the SALMA Study

Acute myeloid leukemia (AML) is a heterogeneous clonal myeloid neoplasm where abnormal proliferation and impaired differentiation of hematopoietic stem and myeloid progenitor cells impedes normal hematopoiesis. Sulfasalazine (SSZ) is a broadly available, well tolerated anti-inflammatory medicine approved for the treatment of ulcerative colitis and rheumatoid arthritis. Intact SSZ, but not its metabolites 5-aminosalicylic acid and sulfapyridine, competitively inhibits xCT.21 SSZ is thus an ideal candidate for drug repurposing in AML.The purpose of this phase I study is to evaluate the safety and feasibility of such strategy, provide preliminary signals of efficacy, and identify potential biomarkers

Being tested
Sulfasalazine
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.

  • SulfasalazineDrug

    Sulfazalazine 500mg-tablets ; 7 dose levels explored in the phase I part of the trial.

Study groups in NCT05580861
Study groupRoleWhat they receive
Cohort : Patients with acute myeloid leukemiaExperimentalNot described
Receives: Drug: Sulfasalazine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity (for phase I part of the trial)

    Defined as any of the following events:

    • Prolonged myelosuppression defined as Grade ≥ 3 Neutropenia or Thrombocytopenia on Day 42 from start of therapy or later without evidence of leukemia (assessed by bone marrow aspiration and/or biopsy)
    • Grade ≥3 hemorrhages until day 42.
    • Grade ≥3 non- hematological toxicity until day 42 with the exception of: Grade 3 infection, grade 3 fever with neutropenia (NB. grade 4 infections and grade 4 fever with neutropenia are considered as DLTs), Grade ≥3 nausea, vomiting or diarrhea that can be managed to ≤ Grade 2 within 72 hours of symptomatic treatment, Grade ≥3 asymptomatic liver enzymes elevation that improves to ≤ Grade 2 within 72 hours of onset, Grade ≥3 tumor lysis syndrome that resolves within 72 hours of onset with medical treatment

    Measured: 42 days

  2. Minimal Residual Disease (MRD)-negative Complete Response (for phase II part of the trial)

    Defined as:

    • Complete Remission CR or CRi (CR with incomplete hematologic recovery, meaning CR with platelet count <100,000/μL or absolute neutrophil count <1000/μL) and CRh (CR with partial hematologic recovery, meaning CR not fulfilling CR or CRi peripheral blood count criteria but with platelet count >50,000/μL AND absolute neutrophil count >500/μL).
    • MRD-negativity is defined as an 8-color bone marrow FCM MRD < 0.1% at EOI.
    • Of note, NPM1 (nucleoplasmin)-transcript based MRD in the Bone Marrow and Peripheral Blood will be carried as exploratory endpoint in NPM1-mutated patients.

    Measured: Day 28 to 42

Secondary outcomes (25)

  1. Adverse events

    Adverse events (AE), treatment emergent adverse events (TEAE) and treatment-related TEAEs will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: Month 12

  2. Peak plasma concentration (Cmax) of Sulfazalazine

    Pharmacokinetics of Sulfazalazine in terms of Peak Plasma Concentration (Cmax), in the phase I part of the study

    Measured: Day 1, 4 and 15

  3. Time of peak plasma concentration (Tmax) of Sulfazalazine

    Pharmacokinetics of Sulfazalazine in terms of Time of peak plasma concentration (Tmax) of Sulfazalazine, in the phase I part of the study

    Measured: Day 1, 4 and 15

  4. Area under the plasma concentration versus time curve (AUC) for Sulfazalazine

    Pharmacokinetics of Sulfazalazine in terms of area under the plasma concentration versus time curve (AUC), in the phase I part of the study

    Measured: Day 1, 4 and 15

  5. Clearance (Cl) of Sulfazalazine

    Pharmacokinetics of Sulfazalazine in terms of clearance (Cl), in the phase I part of the study

    Measured: Day 1, 4 and 15

  6. Mean residence time (MRT) of Sulfazalazine

    Pharmacokinetics of Sulfazalazine in terms of mean residence time (MRT), in the phase I part of the study

    Measured: Day 1, 4 and 15

  7. Distribution volume (Vd/F) of Sulfazalazine

    Pharmacokinetics of Sulfazalazine in terms of distribution volume (Vd/F), in the phase I part of the study

    Measured: Day 1, 4 and 15

  8. Plasma levels of malondialdehyde

    Pharmacodynamics with plasma levels of malondialdehyde (MDA)

    Measured: Day 1, 2

  9. Plasma levels of glutathione

    Pharmacodynamics with plasma levels of glutathione (reduced/oxidized)

    Measured: Day 1, 2

  10. Reactive Oxygen Species (ROS) levels of peripheral blood mononuclear cells

    In patients with circulating leukemic cells, ROS levels of peripheral blood mononuclear cells by flow cytometry

    Measured: Day 1, 2

  11. Response

    Response at end of induction assessment (day 28-42) as per European LeukemiaNet (ELN) Criteria.

    Measured: End of induction treatment - day 28 to 42

  12. Nucleophosmin (NPM1)-transcript based Minimal Residual Disease (MRD)

    NPM1-transcript based MRD in the bone marrow and peripheral blood in NPM1-mutated patients

    Measured: End of induction treatment - day 28 to 42

  13. Next-generation sequencing (NGS)-based Minimal Residual Disease (MRD)

    NGS-based MRD in all patients

    Measured: End of induction treatment - day 28 to 42

  14. Event-free survival

    Event-free survival (EFS) defined as the time between inclusion and the first of the following events:

    • Non achievement of hematologic response (including complete response (CR), CR with incomplete hematologic recovery (CRi), CR with partial hematologic recovery (CRh))
    • Hematologic relapse or progressive disease
    • Initiation of any subsequent anti-leukemic therapy (excluding hydroxyurea)
    • Death

    Measured: 12 months

  15. Duration of response (DOR)

    Duration of response (DOR)

    Measured: 12 months

  16. Relapse-free survival

    Relapse-free survival (RFS) defined as the time between inclusion and the first of the following events:

    • Hematologic relapse or progressive disease
    • Death

    Measured: 12 months

  17. Overall survival

    Overall survival (OS), defined as the time between inclusion and death

    Measured: 12 months

  18. Incidence of subsequent allogeneic hematopoietic stem cell transplant

    Incidence of subsequent allogeneic hematopoietic stem cell transplant (HSCT), overall and in responding patients specifically

    Measured: 12 months

  19. Targeted gene sequencing

    Targeted sequencing of a panel of genes recurrently mutated in AML, on bone marrow and peripheral blood samples

    Measured: Inclusion and end of induction (day 28 to 42)

  20. SLC7A11 expression

    SLC7A11 expression by flow cytometry (FCM) and/or western blot (WB), on bone marrow and peripheral blood samples

    Measured: Inclusion and end of induction (day 28 to 42)

  21. Genotyping of ABCG2 rs2231142 polymorphisms

    Genotyping of ABCG2 rs2231142 polymorphisms, on bone marrow and peripheral blood samples, in consenting patients

    Measured: Inclusion and end of induction (day 28 to 42)

  22. NAT2 genotype

    NAT2 genotype (NAT2*4, NAT2*5B, NAT2*6A, NAT2*7B), in consenting patients

    Measured: Inclusion and end of induction (day 28 to 42)

  23. RNA-based antioxidogram

    RNA-based expression patterns of major enzymes involved in the antioxidant cellular response (as described in Picou et al, Blood Advances 2019)

    Measured: Inclusion and end of induction (day 28 to 42)

  24. Antioxidant score

    Antioxidant score is a summary measure of expression patterns of major enzymes involved in the antioxidant cellular response (as described in Picou et al, Blood Advances 2019)

    Measured: Inclusion and end of induction (day 28 to 42)

  25. Expression of NRF2 target genes

    Expression of NRF2 target genes (NRF2 score) on bone marrow samples

    Measured: Inclusion and end of induction (day 28 to 42)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2022
  2. Study start17 May 2023
  3. Primary completionNov 2025 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

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
Phase I dose-finding design unsing the continueal reassessment method, followed by a dose expansion cohort using a Simon's phase II design.
Masking
None (open label)
Enrolment
64 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05580861
Sponsor's protocol ID
APHP211176
Acronym
SALMA
Status last verified
May 2024
First submitted
26 Sep 2022
Last updated
29 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sulfasalazine in people with Acute Myeloid Leukemia, run by Assistance Publique - Hôpitaux de Paris at 13 sites in France.

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 8 inclusion and 34 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: looking for participants now, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Raphaël Itzykson, Pr (1 42 49 96 43 ext. +33, raphael.itzykson@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (for phase I part of the trial) (time frame: 42 days). 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?

On the ClinicalTrials.gov record for NCT05580861.

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 29 May 2024.

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