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Study of IACS-010759 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML)

This study is currently recruiting participants.
Verified September 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02882321
First Posted: August 29, 2016
Last Update Posted: September 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

This clinical research study has 2 parts: dose escalation and dose expansion.

The goal of dose escalation in this clinical research study is to find the best dose of IACS-010759 that can be given to patients with relapsed or refractory AML.

The goal of dose expansion in this clinical research study is to learn if the dose of IACS-010759 found in the dose escalation part of the study is the best dose to use in future studies using IACS-010759 in patients with AML.

The safety and tolerability of this drug will also be studied.

This is the first study using IACS-010759 in humans.

This is an investigational study. IACS-010759 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.

Up to 48 participants will take part in this study. All will be enrolled at MD Anderson.


Condition Intervention Phase
Acute Myeloid Leukemia Drug: IACS-010759 Behavioral: Phone Call Follow Up Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of IACS-010759 in Subjects With Relapsed or Refractory Acute Myeloid

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of IACS-010759 [ Time Frame: 21 days ]

    MTD defined as the highest dose studied for which observed incidence of dose limiting toxicity (DLT) is less than 33%. Frequencies of toxicities tabulated according to the NCI Common Toxicity Criteria version 4.03.

    DLT defined as a clinically significant non-hematologic adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and is possibly, probably or definitely related to the study drug and occurring during the first cycle.



Secondary Outcome Measures:
  • Overall Response Rate (ORR) as Determined by Complete Remission (CR), Complete Remission with Incomplete Hematological Recovery (CRi), Partial Remission (PR), Morphologic Leukemia-Free State (MLFS), and Hematologic Improvement (HI): [ Time Frame: 63 days ]
    Participants undergo bone marrow aspirate and/or biopsy.

  • Food Effect on PK of IACS-010759 [ Time Frame: Start of study drug up to 30 days after study drug stopped ]
    PK determined by blood draws.


Estimated Enrollment: 48
Actual Study Start Date: September 29, 2016
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IACS-010759

Dose Escalation Phase: IACS-010759 administered orally daily on a 21-day schedule, with the exception that the first cycle for each subject contains a 7-day single dose lead-in. Treatment administered as an inpatient for 24 hours on day 1 and then starting on day 8 for the next 7 days for all enrolled subjects. Starting on day 8 of cycle 1, dosing is on a 21 day schedule until confirmed progressive disease (PD), initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue.

Dose Expansion Phase: Subjects in the expansion phase treated at the RP2D level determined in the dose-escalation phase.

Drug: IACS-010759

Dose Escalation Phase Starting Dose: 0.5 mg by mouth daily on a 21-day schedule.

Dose Expansion Phase Starting Dose: Maximum tolerated dose from Dose Escalation Phase.

Behavioral: Phone Call Follow Up
If participant's disease appears to be responding to study drug, member of the study staff calls every 3-6 months for up to 5 years.
Experimental: Food Effect on PK of IACS-010759

As part of the expansion phase, the effect of a high fat meal on the PK of IACS-010759 (Food Effect) evaluated in a total of 6 subjects. After the first 6 subjects have been enrolled in the expansion cohort, the next 6 subjects enrolled in the Food Effect cohort.

Subjects in the expansion phase treated at the RP2D level determined in the dose-escalation phase.

Drug: IACS-010759

Dose Escalation Phase Starting Dose: 0.5 mg by mouth daily on a 21-day schedule.

Dose Expansion Phase Starting Dose: Maximum tolerated dose from Dose Escalation Phase.

Behavioral: Phone Call Follow Up
If participant's disease appears to be responding to study drug, member of the study staff calls every 3-6 months for up to 5 years.

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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; refractory defined as failure to achieve CR to standard induction therapy, such as "7 and 3", high dose ara-C-containing regimen or a hypomethylating agent): 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.
  2. Eastern Cooperative Oncology Group (ECOG) </= 2
  3. Patients who have had prior SCT are eligible if they have a relapse > 6 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.
  4. 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.
  5. Adequate renal and hepatic function: 1) Serum creatinine </= 1.5 X ULN or calculated creatinine clearance >/= 45 mL/minute per the Cockcroft-Gault formula or MDRD formula; 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).
  6. 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).
  7. 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.
  8. Age >/= 18 years.
  9. 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 for cytotoxic agents and biological/immune-based therapies or at least 5 half-lives for cytotoxic/noncytotoxic 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 (IT) 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.
  10. 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;
  11. #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.
  12. #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.
  13. Able and willing to give valid written informed consent.

Exclusion Criteria:

  1. Prior exposure to IACS-010759 or other oxidative phosphorylation Inhibitors.
  2. 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.
  3. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery from the surgical procedure
  4. Presence of >/= CTCAE grade 2 toxicity (except alopecia or peripheral neuropathy) due to prior cancer therapy.
  5. Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV).
  6. Active uncontrolled infection. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.
  7. 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.
  8. Lactate levels > 2 mmol/L and or and serum pH <7.35 at screening.
  9. Subject currently being treated with biguanides or other agents known to increase risk of lactic acidosis.
  10. 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.
  11. Subjects with uncontrolled Type I or II diabetes mellitus
  12. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  13. Women who are breast-feeding or pregnant as evidenced by positive urine pregnancy test done within 72 hours of first dosing.
  14. 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
  15. Acute promyelocytic leukemia.
  16. 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02882321


Contacts
Contact: Marina Konopleva, MD, PHD 713-794-1628

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
The Leukemia and Lymphoma Society
Investigators
Principal Investigator: Marina Konopleva, MD, PHD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02882321     History of Changes
Other Study ID Numbers: 2016-0250
NCI-2017-00620 ( Registry Identifier: NCI CTRP )
First Submitted: August 24, 2016
First Posted: August 29, 2016
Last Update Posted: September 13, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant Tumor of Lymphoid Hemopoietic and Related Tissue
Acute myeloid leukemia
AML
Relapsed/Refractory
IACS-010759
Phone Call follow up

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms