AzTrials
AzTrials

Recurrent Acute Myeloid LeukemiaPhase 1NCT02882321

Oxidative Phosphorylation Inhibitor IACS-010759 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing Oxidative Phosphorylation Inhibitor IACS-010759 and Pharmacological Study in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and best dose of oxidative phosphorylation inhibitor IACS-010759 in treating patients with acute myeloid leukemia that has come back or does not respond to treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Oxidative Phosphorylation Inhibitor IACS-010759 and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
29 Sep 2016to 15 Apr 2022
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects with AML should have failed any prior induction therapy regimen or have relapsed after prior therapy (defined as patients in first relapse and less than 12 months from diagnosis [short first remission] or in second or later relapse: Dose-escalation phase: Subjects with confirmed relapsed or refractory AML and no available treatment options with known benefit. Expansion phase: Subjects with relapsed/refractory AML who have failed therapy with up to one prior salvage regimen and no available treatment options with known benefit Exception: SCT or stem cell therapy for subjects who previously underwent SCT/stem cell therapy, and are currently in remission will not be considered a salvage regimen.
  • Eastern Cooperative Oncology Group (ECOG) </= 2
  • Patients who have had prior SCT are eligible if they have a relapse > 3 months since autologous or allogeneic stem cell transplantation provided, 1) No clinically significant active graft-versus-host disease (GVHD > grade 1); 2) No treatment with high dose steroids for GVHD (i.e. >20 mg Prednisolone or equivalent per day); 3) No treatment with immunosuppressive drugs with the exception of cyclosporine and tacrolimus.
  • Subjects with history of central nervous system (CNS) disease are allowed if at the time of day 1 of the study there is no evidence of active CNS disease as documented by negative imaging or spinal fluid analysis carried out at least 2 weeks prior to the first study drug administration in a subject with no clinical signs of CNS disease.
  • Adequate renal and hepatic function: 1) Serum creatinine </= 2.0 X ULN; 2) Total bilirubin </= 2 times the upper limit of normal (ULN) (or </= 3.0 x ULN if deemed to be elevated due to Gilbert's disease or leukemia); 3) Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) </= 2.5 times ULN (</= 5.0 x ULN if due to leukemic involvement).
  • Negative urine pregnancy test within 72 hours prior to the first dose of study therapy for women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post- menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months).
Show all 13Show fewer
  • Have been informed of other treatment options and is not a candidate for standard treatment options or stem cell transplant at the time of enrollment.
  • Age >/= 18 years.
  • In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of IACS-010759 administration will be at least 2 weeks or 5 half-lives (whichever is shorter) for cytotoxic/noncytotoxic agents and biological/immune therapies, including investigational agents. The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochures, or drug-administration manuals) and will be documented in the protocol eligibility document. The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intrathecal therapy for subjects with controlled CNS leukemia at the discretion of the PI and with the agreement of the Sponsor. (2) Use of hydroxyurea for subjects with rapidly proliferative disease is allowed before the start of study therapy and for the first 2 cycles on therapy. These medications will be recorded in the case-report form.
  • Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include: 1) Total abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; 2) Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
  • #10 continued: 3) Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject;4) Combination of any of the two following (a+b or a+c or b+c): a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception;b. Placement of an intrauterine device (IUD) or intrauterine system (IUS); c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository. In case of use of oral contraception, women should have been stable on the same pill before taking study treatment.
  • #11 continued: Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  • Able and willing to give valid written informed consent.

Who cannot join

  • Prior exposure to IACS-010759 or other oxidative phosphorylation Inhibitors.
  • Unstable cardiovascular function: 1) Symptomatic ischemia, or 2) Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or 3) Congestive heart failure (CHF) NYHA Class >/= 3, or 4) Myocardial infarction (MI) within 6 months; 5) Left ventricular ejection fraction < 40 %; 6) hypertension > 160 mm Hg systolic or > 100 mm Hg diastolic with or without antihypertensive therapy.
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery from the surgical procedure
  • Presence of >/= CTCAE grade 2 toxicity (except alopecia or peripheral neuropathy) due to prior cancer therapy.
  • Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV).
  • Active uncontrolled infection. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.
Show all 17Show fewer
  • Participation in any other clinical trial involving another investigational agent for the treatment of AML within 2 weeks prior to day 1 of the study or at least 5 half-lives of the investigational agent, whichever is shorter.
  • Lactate levels > 2 mmol/L and or and serum pH <7.35 at screening.
  • Subject currently being treated with biguanides or other agents known to increase risk of lactic acidosis.
  • Subject has significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhea associated with intestinal malabsorption, Crohn's disease, and/or prior surgical procedures affecting absorption or requirement for intravenous (IV) alimentation.
  • Subjects with uncontrolled Type I or II diabetes mellitus
  • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Women who are breast-feeding or pregnant as evidenced by positive urine pregnancy test done within 72 hours of first dosing.
  • Subject has a concurrent active malignancy under treatment, with the exception of: -Adequately treated carcinoma in situ of the breast or cervix uteri; -Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; -Low-grade, early-stage prostate cancer with no requirement for therapy; -Previous malignancy confined
  • Acute promyelocytic leukemia.
  • Any concomitant disease or condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
  • Subjects with >/= grade 1 peripheral neuropathy at screening.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase 1 Study of IACS-010759 in Subjects With Relapsed or Refractory AML

This phase I trial studies the side effects and best dose of oxidative phosphorylation inhibitor IACS-010759 in treating patients with acute myeloid leukemia that has come back or does not respond to treatment. Oxidative phosphorylation inhibitor IACS-010759 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined the study. Up to 6 groups of 3-6 participants will be enrolled in the dose escalation part of the study. Up to 18 participants will be enrolled in dose expansion.

OUTLINE: This is a dose-escalation study.

INDUCTION PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 orally (PO) once daily (QD) on days 1-7.

MAINTENANCE PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 8 and 15 of course 1 and on days 1, 8, and 15 of subsequent courses. Treatment repeats every 21 days for subsequent courses for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may receive additional courses of oxidative phosphorylation inhibitor IACS-010759 at the discretion of study doctor.

After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.

If you are enrolled in dose escalation, the dose of IACS-010759 you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of IACS-010759. Each new group will receive a higher dose of IACS-010759 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of IACS-010759 is found.

If you are enrolled in the dose expansion part of the study, you will receive the dose level of IACS-010759 that was found to be the best dose in the escalation part of the study.

In the dose expansion part of the study, 6 participants will also be enrolled in a food-effect group (described in more detail below) to help researchers understand the effects of taking the study drug with food.

Study Drug Administration Each study cycle is 21 days. Cycle 1 only is 28 days. You will take IACS-010759 by mouth one (1) time every day. On Day 1 of Cycle 1 only, you will take your first dose of IACS-010759 and then wait 7 days to take your next dose. Starting on Day 8 of Cycle 1, you will take the study drug every day for the next 21 days.

You will be admitted to the hospital on Day 1 of Cycle 1 for 24 hours and on Day 8 of Cycle 1 for 7 days. This is done so that you can be checked on for any side effects.

Length of Study You may continue to take IACS-010759 for up to 12 cycles. If the doctor thinks it is in your best interest, you may be able to continue receiving the study drug beyond 12 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Being tested
Oxidative Phosphorylation Inhibitor IACS-010759, Pharmacological Study
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.

  • Oxidative Phosphorylation Inhibitor IACS-010759Drug

    Also called IACS-010759, OXPHOS Inhibitor IACS-010759

    Given PO

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02882321
Study groupRoleWhat they receive
Treatment (oxidative phosphorylation inhibitor IACS-010759) Cohort 1ExperimentalIACS-010759 Starting dose: 0.5 mg INDUCTION PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 1-7.
Receives: Drug: Oxidative Phosphorylation Inhibitor IACS-010759
Treatment (oxidative phosphorylation inhibitor IACS-010759) Cohort 2ExperimentalIACS-010759 Starting dose: 1 mg INDUCTION PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 1-7.
Receives: Drug: Oxidative Phosphorylation Inhibitor IACS-010759
Treatment (oxidative phosphorylation inhibitor IACS-010759) Cohort 3ExperimentalIACS-010759 Starting dose: 2 mg INDUCTION PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 1-7. MAINTENANCE PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 8 and 15 of course 1 and on days 1, 8, and 15 of subsequent courses. Treatment repeats every 21 days for subsequent courses for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may receive additional courses of oxidative phosphorylation inhibitor IACS-010759 at the discretion of study doctor.
Receives: Drug: Oxidative Phosphorylation Inhibitor IACS-010759; Other: Pharmacological Study
Treatment (oxidative phosphorylation inhibitor IACS-010759) Cohort 4ExperimentalIACS-010759 Starting dose: 2.5 mg INDUCTION PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 1-7. MAINTENANCE PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 8 and 15 of course 1 and on days 1, 8, and 15 of subsequent courses. Treatment repeats every 21 days for subsequent courses for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may receive additional courses of oxidative phosphorylation inhibitor IACS-010759 at the discretion of study doctor.
Receives: Drug: Oxidative Phosphorylation Inhibitor IACS-010759; Other: Pharmacological Study

What is being measured

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

  1. Maximum Tolerated Dose (MTD) Defined as the Highest Dose Studied for Which the Observed Incidence of Dose Limiting Toxicities (DLT) is Less Than 33%

    Will be assessed according to National Cancer Institute Common Toxicity Criteria version 4.03.

    Measured: Up to 28 days

Secondary outcomes (4)

  1. Participants With a Response

    Response is Complete Response (CR) + Complete Response with Incomplete Blood Count Recovery (CRi) + Partial Response (PR) + Morphologic Leukemia -Free State (MLFS): CR is Bone marrow blasts < 5%; absence of circulating blasts and blasts with Auer rods; absence of extra-medullary disease; ANC > 1.0 x 10^9/L; platelet count >/= 100 x 10^9/L. CRi is CR except for ANC </= 1.0 x 10^9 or platelet count , 100 x 10^9/L. PR is decreased bone marrow blast % by at least 50% to a value of 5% to 25% and ANC >/= 1.0 x 10^9/L; platelet count >/= 100 x 10^9/L. MLFS is Bone marrow blasts < 5%; abcence of blasts with Auer rods; absence of extra-medullary disease; no hematologic recovery required.

    Measured: Up to 5 years

  2. Duration of Response

    Duration of Response: length of time from the first objective evidence of response to the first objective evidence of disease progression.

    Measured: Up to 5 years

  3. Progression-free Survival

    Progression-Free Survival: length of time (up to 5 years) from the date of first treatment to the first objective evidence of disease progression or death, whichever is earlier.

    Measured: Up to 5 years

  4. Overall Survival

    Overall Survival: length of time from the date of first administration of study drug to the date of death from any cause.

    Measured: Up to 5 years

Timeline

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

  1. First posted29 Aug 2016 (estimated)
  2. Study start29 Sep 2016
  3. Primary completion15 Apr 2022
  4. Study completion15 Apr 2022

Why it stopped: The study was terminated by the Sponsor for apparent lack of effectiveness.

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02882321
Sponsor's protocol ID
2016-0250
Other IDs
NCI-2017-00620, 2016-0250
Status last verified
Jun 2023
First submitted
24 Aug 2016
Last updated
15 Jun 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Yap TA, Daver N, Mahendra M, Zhang J, Kamiya-Matsuoka C, Meric-Bernstam F, Kantarjian HM, Ravandi F, Collins ME, Francesco MED, Dumbrava EE, Fu S, Gao S, Gay JP, Gera S, Han J, Hong DS, Jabbour EJ, Ju Z, Karp DD, Lodi A, Molina JR, Baran N, Naing A, Ohanian M, Pant S, Pemmaraju N, Bose P, Piha-Paul SA, Rodon J, Salguero C, Sasaki K, Singh AK, Subbiah V, Tsimberidou AM, Xu QA, Yilmaz M, Zhang Q, Li Y, Bristow CA, Bhattacharjee MB, Tiziani S, Heffernan TP, Vellano CP, Jones P, Heijnen CJ, Kavelaars A, Marszalek JR, Konopleva M. Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials. Nat Med. 2023 Jan;29(1):115-126. doi: 10.1038/s41591-022-02103-8. Epub 2023 Jan 19.

    PubMed 36658425

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oxidative Phosphorylation Inhibitor IACS-010759 and Pharmacological Study in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 13 inclusion and 17 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 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 15 Jun 2023). 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?

Maximum Tolerated Dose (MTD) Defined as the Highest Dose Studied for Which the Observed Incidence of Dose Limiting Toxicities (DLT) is Less Than 33% (time frame: Up to 28 days). 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 NCT02882321, which also lists 1 linked publication.

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 15 Jun 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in