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Granulocytic SarcomaPhase 1NCT02484391

CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Granulocytic Sarcoma

A Phase 1 study testing 6,8-Bis(benzylthio)octanoic Acid, Cytarabine and Hematopoietic Cell Transplantation in people with Granulocytic Sarcoma and Recurrent Adult Acute Myeloid Leukemia, run by Wake Forest University Health Sciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This pilot phase I trial studies how well CPI-613 (6,8-bis[benzylthio]octanoic acid), cytarabine, and mitoxantrone hydrochloride work in treating patients with acute myeloid leukemia or granulocytic sarcoma (a malignant, green-colored tumor of myeloid cells [a type of immature white blood cell]) that has returned… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
6,8-Bis(benzylthio)octanoic Acid, Cytarabine and Hematopoietic Cell Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited States
Study dates
Sep 2015to 2 Feb 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

  • Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia or granulocytic sarcoma
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 3
  • Expected survival > 3 months
  • Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
  • Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists
  • Mentally competent, ability to understand and willingness to sign the informed consent form
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  • No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy within the 2 weeks prior to treatment with CPI-613; hydroxyurea and oral tyrosine kinase inhibitors being used without grade =< 2 toxicity can be taken until day 1 of therapy; patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, non-hematologic, non-infectious toxicities from prior treatment =< grade 2 are eligible, but must be documented as such
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3 x UNL (=< 5 x upper limit of normal [ULN] if liver metastases present)
  • Bilirubin =< 1.5 x UNL
  • Serum creatinine =< 1.5 mg/dL or 133 umol/L
  • International normalized ratio or INR must be < 1.5
  • Left ventricular ejection fraction (by transthoracic echocardiography [TTE], multigated acquisition scan [MUGA] or cardiac magnetic resonance imaging [MRI]) sufficient to safely administer mitoxantrone as determined by the treating physician

Who cannot join

  • Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity
  • Patients with active central nervous system (CNS) or epidural tumor
  • Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
  • Pregnant women, or women of child-bearing potential not using reliable means of contraception
  • Lactating females
  • Fertile men unwilling to practice contraceptive methods during the study period
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  • Life expectancy less than 3 months
  • Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
  • Unwilling or unable to follow protocol requirements
  • Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly); patients with any amount of clinically significant pericardial effusion
  • Active heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, uncontrolled arrhythmias, or symptomatic congestive heart failure
  • Evidence of ongoing, uncontrolled infection
  • Patients with known human immunodeficiency virus (HIV) infection
  • Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 2 weeks prior to initiation of CPI-613 treatment (the use of Hydrea is allowed)
  • Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment
  • Requirement for immediate palliative treatment of any kind including surgery
  • Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months
  • A history of additional risk factors for torsade de pointes (e.g., clinically significant heart failure, hypokalemia, family history of long QT syndrome)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Comprehensive Cancer Center of Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: An Open Label Study to Evaluate the Feasibility of CPI-613 Given With High Dose Cytarabine and Mitoxantrone in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

This pilot phase I trial studies how well CPI-613 (6,8-bis[benzylthio]octanoic acid), cytarabine, and mitoxantrone hydrochloride work in treating patients with acute myeloid leukemia or granulocytic sarcoma (a malignant, green-colored tumor of myeloid cells [a type of immature white blood cell]) that has returned (relapsed) or that does not respond to treatment (refractory). 6,8-bis(benzylthio)octanoic acid is thought to kill cancer cells by turning off their mitochondria. Mitochondria are used by cancer cells to produce energy and are the building blocks needed to make more cancer cells. By shutting off these mitochondria, 6,8-bis(benzylthio)octanoic acid deprives the cancer cells of energy and other supplies that they need to survive and grow in the body. Drugs used in chemotherapy, such as cytarabine and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving 6,8-bis(benzylthio)octanoic acid together with cytarabine and mitoxantrone hydrochloride may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the feasibility of CPI-613 when administered with high dose cytarabine, and mitoxantrone (mitoxantrone hydrochloride) in all three phases of salvage therapy (induction, consolidation and maintenance).

SECONDARY OBJECTIVES:

  1. To observe the response rate (complete remission [CR], and CR with incomplete recovery [CRi]) of CPI-613 in combination with high dose cytarabine and mitoxantrone.

II. To observe the overall survival of patients treated with CPI-613 in combination with high dose cytarabine and mitoxantrone in induction, consolidation and maintenance.

III. To monitor toxicities experienced by patients treated with CPI-613 in combination with high dose cytarabine and mitoxantrone in induction, consolidation and maintenance.

OUTLINE:

SALVAGE INDUCTION COURSE 1: Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-5, cytarabine IV over 3 hours every 12 hours starting on day 3 for 5 doses, and mitoxantrone hydrochloride IV over 15 minutes after the first, third, and fifth doses of cytarabine.

SALVAGE INDUCTION COURSE 2 (OPTIONAL, AT DISCRETION OF TREATING PHYSICIAN): Patients receive 6,8-bis(benzylthio)octanoic acid, cytarabine, and mitoxantrone hydrochloride as in course 1 or an abbreviated second course at the discretion of the treating physician. In the abbreviated course, patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-3, cytarabine IV over 3 hours every 12 hours starting on day 2 for 3 doses, and mitoxantrone hydrochloride IV over 15 minutes after the first and third cytarabine doses.

SALVAGE CONSOLIDATION: Patients achieving response receive up to 2 courses of the abbreviated course of 6,8-bis(benzylthio)octanoic acid, high dose cytarabine, and mitoxantrone hydrochloride. Patients achieving response may undergo stem cell transplant at the discretion of the treating physician. Patients may proceed to maintenance after 1, 2 or no courses of consolidation at the discretion of the treating physician.

MAINTENANCE THERAPY: Patients achieving response receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Being tested
6,8-Bis(benzylthio)octanoic Acid, Cytarabine, Hematopoietic Cell Transplantation, Mitoxantrone Hydrochloride
Medical subject headings
Sarcoma, Myeloid, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 6,8-Bis(benzylthio)octanoic AcidDrug

    Also called Alpha-Lipoic Acid Analogue CPI-613, CPI 613, CPI-613

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine

    Given IV

  • Hematopoietic Cell TransplantationProcedure or surgery

    Also called HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantation

    Undergo stem cell transplant

  • Mitoxantrone HydrochlorideDrug

    Also called CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride

    Given IV

Study groups in NCT02484391
Study groupRoleWhat they receive
Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)ExperimentalSee Detailed Description
Receives: Drug: 6,8-Bis(benzylthio)octanoic Acid; Drug: Cytarabine; Procedure: Hematopoietic Cell Transplantation; Drug: Mitoxantrone Hydrochloride

What is being measured

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

  1. Feasibility of Administering CPI-613 in Combination With High Dose Cytarabine and Mitoxantrone During Induction, Consolidation and Maintenance Therapies, Defined as Percentage of Patients Eligible for Maintenance Therapy Who Complete at Least 3 Courses

    Feasibility is determined by the percentage of patients eligible for maintenance therapy who complete at least 3 cycles, if ≥50% of eligible patients complete 3 cycles of maintenance therapy we will consider this regimen feasible for future study.

    Measured: Up to 12 weeks of maintenance therapy

Secondary outcomes (3)

  1. Frequency of Toxicities Experienced by the Participants, Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0

    The frequency of toxicities experienced by the participants will be presented by type and grade in an effort to monitor and report safety of the treatment. Showing grade 2 and greater event and the highest grade of each type per participant so that a participant is only evaluated once per toxicity type. Reporting events where at least 10% (n=5) of study participants reported a grade 2 or greater event.

    Measured: Up to 6 months

  2. Overall Survival

    Will use Kaplan-Meier estimation to analyze overall survival.

    Measured: Time from enrollment on trial to death from any cause, assessed up to 30 months after completion of therapy

  3. Response Rate (CR and CRi), Assessed by Standard Criteria for AML

    Confidence intervals will be calculated around the estimates of the response rate (CR and CRi). Assuming a response rate of 0.5, with 50 participants, 95 percent confidence intervals can be created with a 0.14 margin of error (0.36, 0.64).

    Measured: Up to 3 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 Jun 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionOct 2018
  4. Study completion2 Feb 2022

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02484391
Sponsor's protocol ID
IRB00033779
Other IDs
NCI-2015-01002, IRB00033779, CCCWFU 22215, P30CA012197
Status last verified
Aug 2024
First submitted
25 Jun 2015
Last updated
19 Sep 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Anderson R, Miller LD, Isom S, Chou JW, Pladna KM, Schramm NJ, Ellis LR, Howard DS, Bhave RR, Manuel M, Dralle S, Lyerly S, Powell BL, Pardee TS. Phase II trial of cytarabine and mitoxantrone with devimistat in acute myeloid leukemia. Nat Commun. 2022 Mar 30;13(1):1673. doi: 10.1038/s41467-022-29039-4.

    PubMed 35354808

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 6,8-Bis(benzylthio)octanoic Acid, Cytarabine and Hematopoietic Cell Transplantation in people with Granulocytic Sarcoma and Recurrent Adult Acute Myeloid Leukemia, run by Wake Forest University Health Sciences 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 12 inclusion and 18 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 19 Sep 2024. 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 19 Sep 2024). 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?

Feasibility of Administering CPI-613 in Combination With High Dose Cytarabine and Mitoxantrone During Induction, Consolidation and Maintenance Therapies, Defined as Percentage of Patients Eligible for Maintenance Therapy Who Complete at Least 3 Courses (time frame: Up to 12 weeks of maintenance therapy). 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 NCT02484391, 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 19 Sep 2024.

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