Clinical Trials /

G-CSF and Continuous Infusion Chemotherapy (CI-GCLAM) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms

NCT04196010

Description:

This phase I trial studies the side effects and best dose of a chemotherapy regimen given by continuous intravenous infusion (CI-GCLAM), and to see how well it works in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory) or other high-grade myeloid neoplasms. Drugs used in CI-GCLAM include G-CSF, cladribine, cytarabine and mitoxantrone, and 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. Continuous intravenous infusion involves giving drugs over a time duration of equal to or more than 24 hours. Giving GCLAM via continuous infusion may result in fewer side effects and have similar effectiveness when compared to giving GCLAM over the shorter standard amount of time.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myeloid Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: G-CSF and Continuous Infusion Chemotherapy (CI-GCLAM) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms
  • Official Title: Dose-Finding (Phase 1) Study of G-CSF and Continuous Infusion Cladribine, Cytarabine and Mitoxantrone (CI-GCLAM) for Adults With Relapsed/Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms Treated at UW/SCCA

Clinical Trial IDs

  • ORG STUDY ID: RG1005551
  • SECONDARY ID: NCI-2019-07696
  • SECONDARY ID: RG1005551
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT04196010

Conditions

  • Myeloid Neoplasm
  • Recurrent Acute Myeloid Leukemia
  • Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Cladribine2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251Treatment (CI-GCLAM)
Cytarabine.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 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-, 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, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453Treatment (CI-GCLAM)
Granulocyte Colony-Stimulating FactorColony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, Granulocyte Colony Stimulating Factor, PluripoietinTreatment (CI-GCLAM)
MitoxantroneDihydroxyanthracenedione, MitozantroneTreatment (CI-GCLAM)

Purpose

This phase I trial studies the side effects and best dose of a chemotherapy regimen given by continuous intravenous infusion (CI-GCLAM), and to see how well it works in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory) or other high-grade myeloid neoplasms. Drugs used in CI-GCLAM include G-CSF, cladribine, cytarabine and mitoxantrone, and 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. Continuous intravenous infusion involves giving drugs over a time duration of equal to or more than 24 hours. Giving GCLAM via continuous infusion may result in fewer side effects and have similar effectiveness when compared to giving GCLAM over the shorter standard amount of time.

Detailed Description

      OUTLINE: This is a dose-escalation study.

      Patients receive CI-GCLAM consisting of cladribine and cytarabine via continuous intravenous
      infusion (CIV) on days 1-2, 1-3, 1-4, 1-5, or 1-6 depending on dose level assignment,
      mitoxantrone via CIV on days 1-2 or 1-3 depending on dose level assignment, and G-CSF on days
      -1 to 2, -1 to 3, -1 to 4, -1 to 5, or -1 to 6 depending dose level assignment. Patients that
      do not achieve a response of minimal residual disease (MRD)-negative complete remission (CR)
      after the first cycle are eligible to receive a second cycle of CI-GCLAM. Treatment continues
      for 2 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CI-GCLAM)ExperimentalPatients receive CI-GCLAM consisting of cladribine and cytarabine via CIV on days 1-2, 1-3, 1-4, 1-5, or 1-6 depending on dose level assignment, mitoxantrone via CIV on days 1-2 or 1-3 depending on dose level assignment, and G-CSF on days -1 to 2, -1 to 3, -1 to 4, -1 to 5, or -1 to 6 depending dose level assignment. Patients that do not achieve a response of MRD-negative CR after the first cycle are eligible to receive a second cycle of CI-GCLAM. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity.
  • Cladribine
  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Mitoxantrone

Eligibility Criteria

        Inclusion Criteria:

          -  Initial presentation with > 10% myeloid blasts in peripheral blood or marrow and,
             after at least one course of induction treatment, now with > 5% blasts in peripheral
             blood or marrow, as assessed by morphology or multiparameter flow cytometry(MFC).
             Outside diagnostic material is acceptable if reviewed here. Patients may never have
             achieved an initial complete remission (< 5% blasts in marrow, absolute neutrophil
             count > 1,000 per microliter, platelet count > 100,000 per microliter) or may have
             relapsed from such a remission. Note that although "AML" is formally denoted by > 20%
             blasts and other high-grade myeloid neoplasm by 10-20% blasts, these two entities
             often have similar prognoses and respond similarly to therapy, with trials at
             University of Washington (UW)/Seattle Cancer Care Alliance (SCCA) as well as MD
             Anderson and various European cooperative groups not distinguishing between AML and
             other high grade myeloid neoplasms

          -  Treatment related mortality (TRM) score < 13.1

          -  Bilirubin < 2.0 mg/dl unless abnormalities thought due to organ infiltration by AML as
             suggested for example by white blood cell (WBC) > 25,000 and rising rapidly

          -  Creatinine < 2.0 mg/dl unless abnormalities thought due to organ infiltration by AML
             as suggested for example by WBC > 25,000 and rising rapidly

          -  Left ventricular ejection fraction > 45% by multigated acquisition scan (MUGA) scan or
             echocardiography

          -  Off any active therapy for AML other than hydroxyurea for at least 1 week prior to
             study registration unless patient has rapidly progressive disease with resolution of
             all grade 2-4 non-hematologic toxicities. Patients with symptoms/signs of
             hyperleukocytosis or WBC > 100,000 and in whom there is a delay in scheduling a MUGA
             scan or other logistical delays can receive two doses of cytarabine (500 mg/m^2 each)

          -  Men and women of childbearing potential must agree to use adequate contraception

          -  Not pregnant or lactating

          -  Not receiving other investigational agents

          -  Provision of informed written consent on study-specific consent form
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:Up to 42 days from start of treatment
Safety Issue:
Description:Will use the Bayesian Optimal Interval ("BOIN") design to select the MTDs for continuous infusion G-CSF, cladribine, cytarabine and mitoxantrone (CI GCLAM).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Trial Keywords

  • Myeloid and Monocytic Leukemia
  • Other Hematopoietic

Last Updated

December 10, 2019