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Myelodysplastic SyndromesPhase 1NCT02995655

CX-01 Combined With Azacitidine in the Treatment of Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

A Phase 1 study testing CX-01, Azacitidine and Bone marrow biopsy in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The investigators hypothesize that CX-01 will disrupt the bone marrow microenvironment and increase the cytotoxic effects of azacitidine on myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) hematopoietic stem cells by disrupting the High-mobility group box protein 1 (HMGB1) interaction with toll-like… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CX-01, Azacitidine and Bone marrow biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
7 Apr 2017to 29 Apr 2019
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • One of the following diagnoses:
  • MDS with International Prostate Symptom Score (IPSS) score of INT-1 or higher and one of the following:
  • Symptomatic anemia with either hemoglobin < 10.0 g/dL or requiring red blood cell (RBC) transfusion
  • Thrombocytopenia with a history of two or more platelet counts < 50,000/µL or a significant hemorrhage requiring platelet transfusions
  • Neutropenia with two or more absolute neutrophil count (ANC) < 1,000/µL
  • Non-M3 AML
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  • Prior treatment with ≥ 4 cycles of a hypomethylating agent (decitabine or azacitidine) without response OR documented disease progression on or after hypomethylating agent therapy
  • Age ≥ 18 years old
  • Adequate renal and hepatic function defined as all of the following:
  • total bilirubin ≤ 1.5 x upper limit of normal (ULN), except in cases of Gilbert's disease
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • serum creatinine < 2.0 x ULN
  • Peripheral blood blast count < 10,000/ µL.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Females must be surgically or biologically sterile or postmenopausal or, if of childbearing potential, must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • Prior allogeneic stem cell transplant
  • Central nervous system (CNS) leukemia
  • Diagnosed with AML and eligible for standard induction chemotherapy or stem cell transplantation.
  • At an increased risk of hemorrhage.
  • Known allergies, hypersensitivity, or intolerance to any form of heparin or azacitidine
  • Presence of significant active bleeding or condition requiring maintenance of a platelet count > 50,000/µL
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  • Presence of any condition requiring any form of anticoagulant therapy (heparin flushes for IV catheter are permitted)
  • Receiving concomitant chemotherapy, radiation therapy, or immunotherapy during the duration of treatment on protocol, or within 21 days prior to enrollment
  • Known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 28 days of study entry.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Pilot Study of CX-01 Combined With Azacitidine in the Treatment of Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

The investigators hypothesize that CX-01 will disrupt the bone marrow microenvironment and increase the cytotoxic effects of azacitidine on myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) hematopoietic stem cells by disrupting the High-mobility group box protein 1 (HMGB1) interaction with toll-like receptor 4 (TLR4) and receptors for advanced glycation end products (RAGE), the CXC chemokine CXCL12/chemokine receptor 4 (CXCR4) axis, and by disrupting other leukocyte and vascular adhesion molecules. In addition, CX-01 may also help promote count recovery after treatment given its affinity for platelet factor-4 (PF4).

The selection of CX-01 dose for study in relapsed or refractory MDS and AML has been based upon the dual requirements to have sufficient drug administered to have potential activity but without clinically significant anticoagulation. The study dose chosen (4 mg/kg bolus followed by 0.25 mg/kg/hour) fulfills both of these criteria. In addition, this dose is expected to result in serum levels of CX-01 which are significantly higher than the IC90 identified in preclinical studies for inhibition of HMGB1-RAGE, toll-like receptor 2 (TLR2) and TLR4 interaction. Therefore, the chosen dose represents a rational balance between effective dosing and safety in thrombocytopenic patients with MDS and AML. This dose was previously established to be safe and tolerable when combined with cytarabine and idarubicin in patients with AML.

Being tested
CX-01, Azacitidine, Bone marrow biopsy, Peripheral blood draw
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute

What participants receive

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

  • CX-01Drug

    Also called 2-O, 3-O desulfated heparin, ODSH

    CX-01 at a dose of 4mg/kg on Day 1 of each 28-day cycle, followed by a continuous intravenous infusion at a dose of 0.25 mg/kg/hour for Days 1 through 7 of each cycle.

  • AzacitidineDrug

    Also called Vidaza®, Ladakamycin

    Azacitidine at a dose of 75mg/m^2 on Days 1-7 of each 28-day cycle.

  • Bone marrow biopsyProcedure or surgery

    -Baseline, day 28 of even-numbered cycle through Cycle 6, and end of study

  • Peripheral blood drawProcedure or surgery

    -Day 1 of each cycle, day 3 of each cycle, day 7 of each cycle, day 28 of every even-numbered cycle through Cycle 6, and end of study

Study groups in NCT02995655
Study groupRoleWhat they receive
CX-01 + AzacitidineExperimental* CX-01 will be administered as a 5-minute bolus infusion at a dose of 4mg/kg on Day 1 of each 28-day cycle, followed by a continuous intravenous infusion at a dose of 0.25 mg/kg/hour for Days 1 through 7 of each cycle. The dose of CX-01 should be calculated based on actual body weight (kg) as measured on Day 1 of each cycle. * Azacitidine will be administered as a 15-minute intravenous infusion at a dose of 75mg/m^2 on Days 1-7 of each 28-day cycle. Azacitidine dose should be calculated based on actual body weight and height to determine BSA. CX-01 may be administered before or after azacitidine, at the discretion of the treating physician. * Up to 6 cycles of treatment allowed
Receives: Drug: CX-01; Drug: Azacitidine; Procedure: Bone marrow biopsy; Procedure: Peripheral blood draw

What is being measured

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

  1. Overall response rate (partial response or higher)

    • Overall response rate = the percentage of patients obtaining partial response or higher
    • Patients will be assessed for response according to modified International Working Group (IWG) criteria

    Measured: 30 days following completion of treatment (estimated to be 28 weeks)

Secondary outcomes (4)

  1. Progression-free survival (PFS)

    • The interval from the date of first dose of study drug to disease progression or death.
    • Described by median time-to-event and a 95% confidence interval, if estimable, using Kaplan-Meier models

    Measured: Up to 5 years

  2. Disease-free survival (DFS)

    • The interval from the date of first documentation of a CR to date of recurrence or death. This is determined only for patients achieving a CR
    • Described by median time-to-event and a 95% confidence interval, if estimable, using Kaplan-Meier models

    Measured: Up to 5 years

  3. Overall survival (OS)

    • The date of first dose of study drug to the date of death from any cause.
    • Described by median time-to-event and a 95% confidence interval, if estimable, using Kaplan-Meier models

    Measured: Up to 5 years

  4. Safety and tolerability of regimen as measured by adverse events tabulated by patient

    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 will be utilized for all toxicity reporting.

    Measured: 30 days following completion of therapy (estimated to be 28 weeks)

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 2016 (estimated)
  2. Study start7 Apr 2017
  3. Primary completion13 Sep 2018
  4. Study completion29 Apr 2019

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
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02995655
Sponsor's protocol ID
201608032
Other IDs
CNTX-CX-01-2016-MDS-1
Status last verified
Dec 2019
First submitted
13 Dec 2016
Last updated
5 Dec 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CX-01, Azacitidine and Bone marrow biopsy in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Washington University School of Medicine 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 16 inclusion and 11 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: finished, as of the sponsor's last update on 5 Dec 2019. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Overall response rate (partial response or higher) (time frame: 30 days following completion of treatment (estimated to be 28 weeks)). 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 NCT02995655.

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 5 Dec 2019.

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