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

NCT02484391 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: IRB00033779NCI-2015-01002CCCWFU 22215P30CA012197
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Granulocytic Sarcoma; Recurrent Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (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.

  Up to 12 weeks of maintenance therapy

Secondary Outcomes (3)

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

  Up to 6 months

• Overall Survival

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

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

  Up to 3 years

Other Outcomes (2)

• Early Mortality (Death Within 60 Days of Beginning of Treatment)

  Up to 60 days

• Complete Response

  Up to 3 years

Study Arms (1)

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

EXPERIMENTAL

See Detailed Description

Drug: 6,8-Bis(benzylthio)octanoic Acid; Drug: Cytarabine; Procedure: Hematopoietic Cell Transplantation; Drug: Mitoxantrone Hydrochloride

Interventions

6,8-Bis(benzylthio)octanoic Acid DRUG

Given IV

Also known as: Alpha-Lipoic Acid Analogue CPI-613, CPI 613, CPI-613

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

Hematopoietic Cell Transplantation PROCEDURE

Undergo stem cell transplant

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantation

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

Mitoxantrone Hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride, Mitoxantrone Dihydrochloride, Mitoxantroni Hydrochloridum, Mitozantrone Hydrochloride, Mitroxone, Neotalem, Novantrone, Onkotrone, Pralifan

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• 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.

  PMID: 35354808 DERIVED

MeSH Terms

Conditions

Sarcoma, Myeloid; Leukemia, Myeloid, Acute

Interventions

devimistat; Cytarabine; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Mitoxantrone

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Connective and Soft Tissue; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Results Point of Contact

• Title: Principal Investigator
• Organization: Wake Forest Baptist Comprehensive Cancer Center

bpowell@wakehealth.edu

336-716-7970

Study Officials

• Bayard Powell

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: June 29, 2015
• Study Start: September 1, 2015
• Primary Completion: October 1, 2018
• Study Completion: February 2, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (1)