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Leukemia, Acute MyelogenousPhase 1NCT02631252

Phase I Study of Mitoxantrone and Etoposide Combined With Hydroxychloroquine, for Relapsed Acute Myelogenous Leukemia

A Phase 1 study testing Hydroxychloroquine, Mitoxantrone and Etoposide in people with Leukemia, Acute Myelogenous, run by Alison Sehgal, MD, MS at 1 site in United States.

Terminated

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

Official record
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Trial summary

This is an open label phase I clinical trial of hydroxychloroquine (HCQ) ,when it is combined with the usual medications for acute myeloid leukemia, mitoxantrone and etoposide. The purpose of this study is to find the safest and most effective dose of hydroxychloroquine with these medications. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Leukemia, Acute Myelogenous
What is being tested?
Hydroxychloroquine, Mitoxantrone and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
18 Aug 2016to 2 Oct 2017
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 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to understand and have the ability to provide written consent
  • Age > 18 years old to <80 years old
  • Patients with AML in the first morphologic relapse as defined by >5% reappearance of leukemia blasts in the bone marrow not attributable to any other cause (Appendix I) who have not yet received chemotherapy for the current relapse
  • Eastern Cooperative Oncology Group Performance Status of 0 -2 (see Appendix II)
  • Adequate organ function
  • Serum creatinine ≤ 1.5 mg/dl and calculated creatinine clearance ≥ 50 mL/min (using the Cockcroft-Gault equation CL creatinine = (140-age) x body mass X 0.85 if female)/72 x creatinine where age is given in years, body mass is given in kg and creatinine is given in mg/dL)
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  • Aspartate aminotransferase (AST) ≤ 5x the upper limit of normal Alanine aminotransferase (ALT) < 5x the upper limit of normal
  • Direct bilirubin ≤ 1.5 mg/dl Note: As many eligible patients will be pancytopenic secondary to their disease or prior treatments, hematologic abnormalities will not be used as a criteria for entry or exclusion
  • Left ventricular ejection fraction (LVEF) ≥50 %
  • Females of child-bearing potential must have a negative pregnancy test during screening and all subjects must agree to use an effective method of contraception. A woman is eligible to enter and participate in the study if she is of:
  • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who has had a hysterectomy or has had a bilateral oophorectomy (ovariectomy).
  • Childbearing potential, has a negative serum pregnancy test during the screening period and agrees to avoid sexual activity or use accepted methods of contraception from screening through follow-up.
  • Men with a female partner of childbearing potential are eligible to enroll and participate in the study if they have had either a prior vasectomy or agree to avoid sexual activity or use appropriate barrier contraception from screening through post-treatment follow-up.

Who cannot join

  • Acute promyelocytic leukemia
  • Prior chemotherapy regimen given for 1st relapse, not including the use of hydroxyurea or plasmapheresis that is used prior to the initiation of chemotherapy.
  • Previous use of mitoxantrone and etoposide combination therapy within the preceding 180 days of screening.
  • Symptomatic central nervous system (CNS) involvement
  • Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
  • History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
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  • Current receiving any other anti neoplastic investigational agents
  • Prior autologous or allogeneic stem cell transplantation
  • Concurrent malignancy. Exceptions: Patients who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with concurrent malignancies that are indolent or definitely treated may be enrolled.
  • Women who are pregnant or breastfeeding
  • Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory or cardiac disease)
  • Inability to take oral medications, due to impaired swallowing ability or poor absorption capacity
  • Known glucose-6-phosphate dehydrogenase (G-6PD) deficiency

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pittsburgh Cancer Institute - Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: A Phase I Study of Combination Chemotherapy With Mitoxantrone and Etoposide (VP-16) Combined With an Autophagy Inhibitor, Hydroxychloroquine (HCQ), for the Treatment of Patients With Relapsed Acute Myelogenous Leukemia (AML)

This is an open label phase I clinical trial of hydroxychloroquine (HCQ) ,when it is combined with the usual medications for acute myeloid leukemia, mitoxantrone and etoposide. The purpose of this study is to find the safest and most effective dose of hydroxychloroquine with these medications. The investigators will be testing to see if it can increase the effectiveness of mitoxantrone and etoposide.

Read the detailed description

Hydroxychloroquine is not FDA (United States Food and Drug Administration) approved for AML and is considered an investigational drug in this study. It has helped make chemotherapy more effective in animals. The investigators will be testing to see if it can increase the effectiveness of mitoxantrone and etoposide. It has been combined with other types of chemotherapy for humans with other types of cancer. Most of the patients were able to take hydroxychloroquine safely at the doses studied in this clinical trial.

Hydroxychloroquine is approved by the FDA for malaria, rheumatoid arthritis, and other autoimmune diseases. Mitoxantrone is approved by the FDA for use in AML, and it is one of the most common drugs used in the treatment of AML. Etoposide is not approved by the FDA for AML. It is approved for small cell lung cancer and testicular cancer. It is commonly used in AML.

The primary objective of this trial is to determine the recommend phase 2 dose (RP2D) for HCQ combined with mitoxantrone and etoposide, while secondary objectives include efficacy estimates of this combination at the RP2D, a safety and tolerability profile of this combination, as well as the correlation of pharmacodynamic assessments of autophagy inhibition with dose and clinical response.

Being tested
Hydroxychloroquine, Mitoxantrone, Etoposide
Keywords
Leukemia, Acute Myelogenous, Phase I, Mitoxantrone, Etoposide, Hydroxychloroquine, Relapsed, Autophagy inhibitor, AML, Relapsed AML
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Recurrence

What participants receive

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

  • HydroxychloroquineDrug

    Also called Plaquenil

    Doses ranging from 600-1400mg daily in divided twice daily doses and administered orally.

  • MitoxantroneDrug

    Also called Dihydroxyanthracenedione, DHAD

    Dose: 10mg/m2 IVPB in 50ml NS

  • EtoposideDrug

    Also called Toposar®, EPEG

    Dose: 100 mg/m2 administered intravenously in 500 ml of 0.9% sodium chloride

Study groups in NCT02631252
Study groupRoleWhat they receive
Open-label, Single-armExperimentalHydroxychloroquine + Mitoxantrone + Etoposide Hydroxychloroquine is given up to 21 days, started concurrently with both Mitoxantrone, administered by IVPB over 15 minutes each day for 5 days and Etoposide, administered intravenously over 2 hours each day for 5 days
Receives: Drug: Hydroxychloroquine; Drug: Mitoxantrone; Drug: Etoposide

What is being measured

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

  1. Select a recommended phase 2 dose (RP2D) for hydroxychloroquine

    Dose limiting toxicity (DLT) that occurs during the first 7 weeks after initiating therapy and is at least possibly related

    Measured: during the first 7 weeks after initiating therapy

Secondary outcomes (8)

  1. Complete Remission (CR)

    Measured: up to 4 weeks after completion of therapy

  2. Overall Survival (OS)

    Measured: until death or last patient contact, up to 5 years

  3. Relapse Free Survival (RFS)

    Measured: until relapse or death, whichever occurs first, or last patient contact, for up to 5 years

  4. Pharmacodynamic Endpoint - Measurement of LC3-1

    Measured: up to 4 weeks after completion of therapy

  5. Pharmacodynamic Endpoint - Measurement of LC3-2

    Measured: up to 4 weeks after completion of therapy

  6. Pharmacodynamic Endpoint - Measurement of p62

    Measured: up to 4 weeks after completion of therapy

  7. Pharmacodynamic Endpoint - Measurement of HMGB1

    Measured: up to 4 weeks after completion of therapy

  8. Pharmacodynamic Endpoint - Measurement of RAGE

    Measured: up to 4 weeks after completion of therapy

Timeline

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

  1. First posted16 Dec 2015 (estimated)
  2. Study start18 Aug 2016
  3. Primary completion17 Sep 2016
  4. Study completion2 Oct 2017

Why it stopped: Inability to accrue

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
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02631252
Sponsor's protocol ID
14-133
Status last verified
Feb 2018
First submitted
9 Dec 2015
Last updated
23 Feb 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hydroxychloroquine, Mitoxantrone and Etoposide in people with Leukemia, Acute Myelogenous, run by Alison Sehgal, MD, MS 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 13 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 23 Feb 2018. 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?

The study was stopped early (reason given: Inability to accrue). Results are not available in the source record.

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?

Select a recommended phase 2 dose (RP2D) for hydroxychloroquine (time frame: during the first 7 weeks after initiating 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 NCT02631252.

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 23 Feb 2018.

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