Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT03318016 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 17-0754.ccNCI-2017-02403
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Determine the maximum tolerated dose (MTD) and toxicity profile of the combination of cyclophosphamide and ATO (Arsenic Trioxide) in subjects with relapsed refractory AML. Determine the efficacy of ATO and cyclophosphamide in this population, as defined by response rate, response duration, event-free survival (EFS) and overall survival (OS). Determine the number of transplant-eligible subjects who are successfully bridged to stem cell transplantation or donor lymphocyte infusion.

Conditions

Acute Myeloid Leukemia; Relapsed/Refractory Acute Myeloid Leukemia

Keywords

Arsenic Trioxide; Cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Reached Maximally Tolerated Dose (MTD) of Cyclophosphamide and ATO

  Number of Participants that were treated in each Cohort in attempt to establish Maximally Tolerated Dose (MTD) of cyclophosphamide with ATO is defined as the highest dose level of 1000 mg/m2. MTD is established when at least 6 participants within a Cohort have responded without toxicity. The trial is organized in a standard, phase I, 3+3 design. The first 3 subjects will be assigned to cohort 1. Per standard trial design, if there are 0/3 dose-limiting toxicities (DLT) in this cohort, the next three subjects will be assigned to cohort 2. This will continue until MTD is established.

  26 months

Secondary Outcomes (1)

• Overall Response Rate (ORR) Using ATO and Cyclophosphamide

  26 months

Study Arms (5)

Cohort -1

EXPERIMENTAL

3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV

Drug: Cyclophosphamide 500 MG

Cohort 1

EXPERIMENTAL

3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV

Drug: Cyclophosphamide 1000 MG

Cohort 2

EXPERIMENTAL

3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV

Drug: Cyclophosphamide 2000 MG

Cohort 3

EXPERIMENTAL

3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV

Drug: Cyclophosphamide 3000 MG

Cohort 4

EXPERIMENTAL

3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV

Drug: Cyclophosphamide 4000 MG

Interventions

Cyclophosphamide 500 MG DRUG

ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 500 mg/m2 on day 4 as a single IV dose along with hydration for a maximum of 6 doses

Also known as: cytophosphane

Cohort -1

Cyclophosphamide 1000 MG DRUG

Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 1000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses

Also known as: cytophosphane

Cohort 1

Cyclophosphamide 2000 MG DRUG

Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 2000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses

Also known as: cytophosphane

Cohort 2

Cyclophosphamide 3000 MG DRUG

Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 3000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses

Also known as: cytophosphane

Cohort 3

Cyclophosphamide 4000 MG DRUG

Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 4000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses

Also known as: cytophosphane

Cohort 4

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• WHO-confirmed AML, other than APL, with no standard treatment options available
• Age 18 years or older
• Relapsed or refractory (resistant) disease, as defined by standard criteria
• Relapsed: Bone marrow blasts ≥5%, reappearance of blasts in the blood, or development of extramedullary disease following achievement of CR/CRi/CRp/MLFS
• Refractory (resistant): Failure to achieve CR/CRi/MLFS in subjects who survive ≥7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination
• \>14 days since any prior therapy for AML excluding hydroxyurea
• Willing and able to understand and voluntarily sign a written informed consent
• Able to adhere to the study visit schedule and other protocol requirements
• Women of childbearing potential must use an acceptable form of birth control for 28 days prior to beginning study treatment, through the duration of study treatment, and for 3 months after discontinuing study treatment.

You may not qualify if:

• New York Heart Association Class III or IV heart failure
• Unstable angina pectoris
• Significant uncontrolled cardiac arrhythmias, including ventricular arrhythmias, congenital long QT syndrome, symptomatic atrial fibrillation, symptomatic bradycardia, right bundle branch block plus left anterior hemiblock or bifasicular block
• QTc \>500 ms, uncorrectable by managing electrolytes and medications, using the QTcF formula in Appendix D.
• Active acute graft vs. host disease ≥ grade 2 or active extensive chronic GVHD
• Relapse after allogeneic stem cell transplantation prior to post-transplant day 30
• Active central nervous system (CNS) involvement of leukemia (lumbar puncture not required to rule out CNS involvement if not suspected)
• Uncontrolled psychiatric illness that would limit compliance with requirements
• Pregnant or breast feeding females
• Laboratory abnormalities:
• Either creatinine \>2.0 mg/dL or creatinine clearance \<30 mL/min
• Total bilirubin \> 3 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome)
• AST or ALT \> 3 x institutional ULN, unless felt to be due to disease involvement
• Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which, in the opinion of the investigator, would compromise the subject's safety or interfere with data interpretation.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Daniel Pollyea, MD Associate Professor
• Organization: University of Colorado Hospital

daniel.pollyea@cuanschutz.edu

720-848-8084

Study Officials

• Daniel Pollyea, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * Cohort -1 (3-6 subjects, if needed): Cyclophosphamide 500 mg/m2 * Cohort 1 (3-6 subjects): Cyclophosphamide 1000 mg/m2 * Cohort 2 (3-6 subjects): Cyclophosphamide 2000 mg/m2 * Cohort 3 (3-6 subjects): Cyclophosphamide 3000 mg/m2 * Cohort 4 (3 subjects): Cyclophosphamide 4000 mg/m2 ATO and Cyclophosphamide will be repeated every 28 days.

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 23, 2017
• Study Start: December 15, 2017
• Primary Completion: January 15, 2020
• Study Completion: January 20, 2021
• Last Updated: August 1, 2024
• Results First Posted: August 1, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)