Untreated Adult Acute Myeloid LeukemiaPhase 1/2NCT02472626

6,8-Bis(Benzylthio)Octanoic Acid, Cytarabine, and Daunorubicin Hydrochloride in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

A Phase 1/2 study testing 6,8-Bis(benzylthio)octanoic Acid, Cytarabine and Daunorubicin Hydrochloride in people with Untreated Adult Acute Myeloid Leukemia, run by Wake Forest University Health Sciences at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 60 years and older
Conditions the study is for: Untreated Adult Acute Myeloid Leukemia
What is being tested?: 6,8-Bis(benzylthio)octanoic Acid, Cytarabine and Daunorubicin Hydrochloride
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: Dec 2015to Jul 2016
Phase: Phase 1/2
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 60 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have histologically or cytologically documented newly diagnosed acute myeloid leukemia (non-acute promyelocytic leukemia [APL]) that has not yet been treated; hydroxyurea (Hydrea) and tretinoin (ATRA) previous treatments are acceptable
Hydroxyurea may be used to control leukocytosis and can be taken until day 1 of therapy; patients with persisting, non-hematologic, non-infectious toxicities from prior treatment =< grade 2 are eligible, but must be documented as such
Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 and fit for induction therapy in the opinion of the treating physician
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal (=< 5 X upper limit of normal [ULN] if liver metastases present)
Bilirubin =< 1.5 X ULN
Creatinine =< 1.5 mg/dL or 133 umol/L

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International normalized ration (INR) < 1.5
Albumin >= 2.0 g/dL
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document

Who cannot join

Patients who have received any therapy other than hydroxyurea with the purpose of treating their AML are not eligible
Patients having received prior radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy within the 2 weeks prior to treatment with CPI-613, or those who have not 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 that have received a chemotherapy regimen with stem cell support in the previous 6 months
Patients with known central nervous system involvement should be excluded from this clinical trial
History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPI-613
Uncontrolled concurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

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Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly); patients with any amount of clinically significant pericardial effusion
Patients with known human immunodeficiency virus (HIV) infection
A history of additional risk factors for Torsade de Pointes (e.g., clinically significant heart failure, hypokalemia, family history of long QT syndrome)
Pregnant women are excluded from this study; breastfeeding should be discontinued

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: A Phase I/II Study of CPI-613 in Combination With Induction/Consolidation in Older AML Patients

This phase I/II trial studies the side effects and the best dose of 6,8-bis(benzylthio)octanoic acid (CPI-613) when given together with cytarabine and daunorubicin hydrochloride and to see how well it works in treating older patients with newly diagnosed acute myeloid leukemia. CPI-613 may kill tumor cells by turning off mitochondria (small structures in the cancer cells that are found in the cytoplasm [fluid that surrounds the cell nucleus]). Mitochondria are used by cancer cells to produce energy and are the building blocks needed to make more tumor cells. By shutting off mitochondria, CPI-613 may deprive the cancer cells of energy and other supplies that they need to survive and grow. Drugs used in chemotherapy, such as cytarabine and daunorubicin 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 CPI-613 together with cytarabine and daunorubicin hydrochloride may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

To determine the maximum tolerated dose (MTD). (Phase I) II. To determine treatment response with the addition of CPI-613 to induction therapy in patients with newly diagnosed acute myeloid leukemia (AML). (Phase II)

SECONDARY OBJECTIVES:

To assess the safety of administering CPI-613 under the proposed study regimen. (Phase I/II) II. To assess survival endpoints of patients receiving the proposed study regimen. (Phase II) III. To assess the rate of allogeneic stem cell transplantation. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of 6,8-bis(benzylthio)octanoic acid followed by a phase II study.

INDUCTION: Patients receive cytarabine intravenously (IV) continuously on days 1-7, daunorubicin hydrochloride IV on days 1-3, and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 3-7. Patients then undergo biopsy on day 14. Patients experiencing significant residual disease receive cytarabine IV continuously on days 1-5, daunorubicin hydrochloride IV on days 1-2, and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5.

CONSOLIDATION: Beginning 42 days later, patients receive cytarabine IV continuously on days 1-16 and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 2-6. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients not undergoing transplant after consolidation receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 14 days and then every 3 months for 2 years.

Conditions: Untreated Adult Acute Myeloid Leukemia
Being tested: 6,8-Bis(benzylthio)octanoic Acid, Cytarabine, Daunorubicin Hydrochloride

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
Daunorubicin HydrochlorideDrug
Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin
Given IV

Study groups in NCT02472626
Study group	Role	What they receive
Treatment (CPI-613, cytarabine, daunorubicin hydrochloride)	Experimental	INDUCTION: Patients receive cytarabine IV continuously on days 1-7, daunorubicin hydrochloride IV on days 1-3, and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 3-7. Patients then undergo biopsy on day 14. Patients experiencing significant residual disease receive cytarabine IV continuously on days 1-5, daunorubicin hydrochloride IV on days 1-2, and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. CONSOLIDATION: Beginning 42 days later, patients receive cytarabine IV continuously on days 1-16 and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 2-6. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients not undergoing transplant after consolidation receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Receives: Drug: 6,8-Bis(benzylthio)octanoic Acid; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride

What is being measured

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

MTD based on the number of observed dose-limiting toxicities as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Dose-limiting toxicity is defined as the occurrence of any clinically relevant, grade >= 3, non-hematologic, non-infectious toxicity attributed as probably or definitely related to 6,8-bis(benzylthio)octanoic acid.
Measured: 14 days
Rate of complete remission (Phase II)
Response rate will be estimated and a 95% confidence interval will be provided.
Measured: Up to 2 years

Secondary outcomes (4)

Incidence of adverse events as assessed by the CTCAE version 4.0 (Phase I/II)
Measured: Up to 14 days post-treatment
Overall survival (OS) (Phase II)
Kaplan-Meier plots will be produced for OS.
Measured: Up to 2 years
Progression-free survival (Phase II)
Kaplan-Meier plots will be produced for disease free survival.
Measured: Up to 2 years
Rate of allogeneic stem cell transplantation (Phase II)
The rate of allogeneic stem cell transplantation will be estimated by the number of transplants as the numerator and all study eligible subjects as the denominator.
Measured: After day 42 post-consolidation therapy

Timeline

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

Dec 2015Jul 2016

First posted16 Jun 2015 (estimated)
Study startDec 2015
Primary completionJul 2016
Study completionJul 2016

Why it stopped: Drug Supply Issues

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Untreated Adult Acute Myeloid LeukemiaStudies of the same condition, open and under way.
More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02472626
Sponsor's protocol ID: IRB00033422
Other IDs: NCI-2015-00890, IRB00033422, CCCWFU 22115, P30CA012197
Status last verified: Jun 2018
First submitted: 12 Jun 2015
Last updated: 3 Jul 2018
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Untreated Adult Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study of CPI-613 in Combination With Induction/Consolidation in Older AML Patients
ClinicalTrials.gov ID: NCT02472626
Acronym / sponsor ID: IRB00033422
Conditions: Untreated Adult Acute Myeloid Leukemia
Phase: Phase 1/2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Drug Supply Issues
Enrolment: 0 participants (actual)
Lead sponsor: Wake Forest University Health SciencesUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: Dec 2015 (actual)
Primary completion: Jul 2016 (actual)
Study completion: Jul 2016 (actual)
First posted: 16 Jun 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To determine the maximum tolerated dose (MTD). (Phase I) II. To determine treatment response with the addition of CPI-613 to induction therapy in patients with newly diagnosed acute myeloid leukemia (AML). (Phase II)

SECONDARY OBJECTIVES:

To assess the safety of administering CPI-613 under the proposed study regimen. (Phase I/II) II. To assess survival endpoints of patients receiving the proposed study regimen. (Phase II) III. To assess the rate of allogeneic stem cell transplantation. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of 6,8-bis(benzylthio)octanoic acid followed by a phase II study.

After completion of study treatment, patients are followed up for 14 days and then every 3 months for 2 years.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (CPI-613, cytarabine, daunorubicin hydrochloride)	Experimental	Drug: 6,8-Bis(benzylthio)octanoic Acid, Drug: Cytarabine, Drug: Daunorubicin HydrochlorideINDUCTION: Patients receive cytarabine IV continuously on days 1-7, daunorubicin hydrochloride IV on days 1-3, and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 3-7. Patients then undergo biopsy on day 14. Patients experiencing significant residual disease receive cytarabine IV continuously on days 1-5, daunorubicin hydrochloride IV on days 1-2, and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. CONSOLIDATION: Beginning 42 days later, patients receive cytarabine IV continuously on days 1-16 and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 2-6. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients not undergoing transplant after consolidation receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Patients must have histologically or cytologically documented newly diagnosed acute myeloid leukemia (non-acute promyelocytic leukemia [APL]) that has not yet been treated; hydroxyurea (Hydrea) and tretinoin (ATRA) previous treatments are acceptable
Hydroxyurea may be used to control leukocytosis and can be taken until day 1 of therapy; patients with persisting, non-hematologic, non-infectious toxicities from prior treatment =< grade 2 are eligible, but must be documented as such
Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 and fit for induction therapy in the opinion of the treating physician
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal (=< 5 X upper limit of normal [ULN] if liver metastases present)
Bilirubin =< 1.5 X ULN

Key exclusion criteria (10 listed)

Patients who have received any therapy other than hydroxyurea with the purpose of treating their AML are not eligible
Patients having received prior radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy within the 2 weeks prior to treatment with CPI-613, or those who have not 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 that have received a chemotherapy regimen with stem cell support in the previous 6 months
Patients with known central nervous system involvement should be excluded from this clinical trial
History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPI-613

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
6,8-Bis(benzylthio)octanoic AcidAlso: Alpha-Lipoic Acid Analogue CPI-613, CPI 613, CPI-613Given IV	Drug	Treatment (CPI-613, cytarabine, daunorubicin hydrochloride)
CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1.beta.-D-ArabinofuranosylcytosineGiven IV	Drug	Treatment (CPI-613, cytarabine, daunorubicin hydrochloride)
Daunorubicin HydrochlorideAlso: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, DaunoblastinGiven IV	Drug	Treatment (CPI-613, cytarabine, daunorubicin hydrochloride)

Primary outcome

MTD based on the number of observed dose-limiting toxicities as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Time frame: 14 days
Dose-limiting toxicity is defined as the occurrence of any clinically relevant, grade >= 3, non-hematologic, non-infectious toxicity attributed as probably or definitely related to 6,8-bis(benzylthio)octanoic acid.
Rate of complete remission (Phase II)
Time frame: Up to 2 years
Response rate will be estimated and a 95% confidence interval will be provided.

4 secondary outcomes

Incidence of adverse events as assessed by the CTCAE version 4.0 (Phase I/II)
Time frame: Up to 14 days post-treatment
Overall survival (OS) (Phase II)
Time frame: Up to 2 years
Progression-free survival (Phase II)
Time frame: Up to 2 years
Rate of allogeneic stem cell transplantation (Phase II)
Time frame: After day 42 post-consolidation therapy

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2018.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Timothy Pardee principal investigator

Wake Forest University Health Sciences

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 10 inclusion and 10 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: withdrawn, as of the sponsor's last update on 3 Jul 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 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

MTD based on the number of observed dose-limiting toxicities as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) (time frame: 14 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 NCT02472626.

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 3 Jul 2018.