Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03318016
Recruitment Status : Completed
First Posted : October 23, 2017
Last Update Posted : April 30, 2021
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

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.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Relapsed/Refractory Acute Myeloid Leukemia Drug: Cyclophosphamide Phase 1

Detailed Description:
This is an open label phase 1 study of fixed dose ATO (Arsenic Trioxide) and escalating doses of cyclophosphamide using a standard 3+3 dose escalation design. All subjects will be treated with sequential cycles of 3 days of ATO at 0.15 mg/kg/d IV followed by Cyclophosphamide as a single IV dose on day 4 along with mesna at a dose equal to the cyclophosphamide (for doses ≥1000 mg/m2) and hydration for a maximum of 6 cycles. ATO and Cyclophosphamide will be repeated every 28-42 days. Treatment will be given inpatient for the first cycle, with the option of outpatient treatment for subsequent cycles. Subjects may remain on study in the absence of disease progression or unacceptable toxicity for a maximum six cycles. Toxicity assessments will be performed continuously; DLT determination will be made based on adverse events (AEs) that occur during cycle 1 (day 1-28). An expansion cohort of ten subjects at the maximum tolerated dose will occur at the conclusion of dose escalation.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
  • 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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Actual Study Start Date : December 15, 2017
Actual Primary Completion Date : January 15, 2020
Actual Study Completion Date : January 20, 2021


Arm Intervention/treatment
Experimental: Cyclophosphamide
  • Cohort -1: Cyclophosphamide 500 mg/m2
  • Cohort 1: Cyclophosphamide 1000 mg/m2
  • Cohort 2: Cyclophosphamide 2000 mg/m2
  • Cohort 3: Cyclophosphamide 3000 mg/m2
  • Cohort 4: Cyclophosphamide 4000 mg/m2
Drug: Cyclophosphamide

ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV dose along with Mesna (in subjects receiving >1000mg/m2 Cy) and hydration for a maximum of 6 doses in the following dose escalation schema:

  • 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




Primary Outcome Measures :
  1. Maximally Tolerated Dose (MTD) of Cyclophosphamide and ATO [ Time Frame: 6 months ]
    MTD is defined as the highest dose level with no more than 1 DLT reported out of 6 DLT-evaluable subjects.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) using ATO and Cyclophosphamide [ Time Frame: minimum 5 years ]
    ORR defined by complete remission/complete remission with incomplete recovery of blood counts (CR/CRi), morphologic leukemia free state (MLFS) and partial responses (PR)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. WHO-confirmed AML, other than APL, with no standard treatment options available
  2. Age 18 years or older
  3. Relapsed or refractory (resistant) disease, as defined by standard criteria7

    • 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
  4. >14 days since any prior therapy for AML excluding hydroxyurea
  5. Willing and able to understand and voluntarily sign a written informed consent
  6. Able to adhere to the study visit schedule and other protocol requirements
  7. 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.

Exclusion Criteria:

  1. New York Heart Association Class III or IV heart failure
  2. Unstable angina pectoris
  3. 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
  4. QTc >500 ms, uncorrectable by managing electrolytes and medications, using the QTcF formula in Appendix D.
  5. Active acute graft vs. host disease ≥ grade 2 or active extensive chronic GVHD
  6. Relapse after allogeneic stem cell transplantation prior to post-transplant day 30
  7. Active central nervous system (CNS) involvement of leukemia (lumbar puncture not required to rule out CNS involvement if not suspected)
  8. Uncontrolled psychiatric illness that would limit compliance with requirements
  9. Pregnant or breast feeding females
  10. Laboratory abnormalities:

    1. Either creatinine >2.0 mg/dL or creatinine clearance <30 mL/min
    2. Total bilirubin > 3 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome)
    3. AST or ALT > 3 x institutional ULN, unless felt to be due to disease involvement
  11. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318016


Locations
Layout table for location information
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Layout table for investigator information
Principal Investigator: Daniel Pollyea, MD University of Colorado, Denver
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03318016    
Other Study ID Numbers: 17-0754.cc
First Posted: October 23, 2017    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
Arsenic Trioxide
Cyclophosphamide
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists