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

NCT04196010 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: RG1005551NCI-2019-0769610310
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of a chemotherapy regimen given by continuous intravenous infusion (CI-CLAM), 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-CLAM include 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 CLAM via continuous infusion may result in fewer side effects and have similar effectiveness when compared to giving CLAM over the shorter standard amount of time.

Conditions

Myeloid Neoplasm; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Keywords

Myeloid and Monocytic Leukemia; Other Hematopoietic

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Will use the Bayesian Optimal Interval ("BOIN") design to select the MTDs for continuous infusion G-CSF, cladribine, cytarabine and mitoxantrone (CI GCLAM).

  Up to 35 days from start of treatment (or 28 days only if a patient presents with an absolute blast count (white blood count x percent blasts) > 50,000 or one that is doubling every 3 days and is > 25,000)

Secondary Outcomes (2)

• Treatment responses

  Up to 5 years post treatment

• Incidence of adverse events

  Up to 5 years post treatment

Study Arms (1)

Treatment (CI-CLAM, G-CSF)

EXPERIMENTAL

Patients receive CI-CLAM 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, and mitoxantrone via CIV on days 1-2 or 1-3 depending on dose level assignment. G-CSF may be added at the discretion of the treating physician, as per standard of care. Patients that do not achieve a response of MRD-negative CR after the first cycle are eligible to receive a second cycle of CI-CLAM. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cladribine; Drug: Cytarabine; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Drug: Mitoxantrone

Interventions

Cladribine DRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Treatment (CI-CLAM, G-CSF)

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-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-28453

Treatment (CI-CLAM, G-CSF)

Recombinant Granulocyte Colony-Stimulating Factor BIOLOGICAL

Given subcutaneously

Also known as: Recombinant Colony-Stimulating Factor 3, rhG-CSF, 143011-72-7

Treatment (CI-CLAM, G-CSF)

Mitoxantrone DRUG

Given IV

Also known as: Dihydroxyanthracenedione, Mitozantrone

Treatment (CI-CLAM, G-CSF)

Eligibility Criteria

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

You may qualify if:

• 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, performed within 6 months prior to consent
• 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, but dosing is ultimately based on physician discretion)
• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute

Interventions

Cladribine; Cytarabine; pegylated granulocyte colony-stimulating factor; Mitoxantrone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Study Officials

• Mary-Beth Percival, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

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: December 10, 2019
• First Posted: December 12, 2019
• Study Start: May 8, 2020
• Primary Completion: October 13, 2021
• Study Completion: October 13, 2021
• Last Updated: December 28, 2023

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)