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

NCT ID: NCT04196010

Last Updated: 2023-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-08
• Study Completion Date: 2021-10-13

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.

Detailed Description

OUTLINE: This is a dose-escalation study.

Patients receive CI-CLAM 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, 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 minimal residual disease (MRD)-negative complete remission (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.

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

Conditions

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

Keywords

Myeloid and Monocytic Leukemia; Other Hematopoietic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (CI-CLAM, G-CSF)

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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IV

Recombinant Granulocyte Colony-Stimulating Factor

Intervention Type: BIOLOGICAL

Given subcutaneously

Mitoxantrone

Intervention Type: DRUG

Given IV

Interventions

Cladribine

Given IV

Intervention Type: DRUG

Cytarabine

Given IV

Intervention Type: DRUG

Recombinant Granulocyte Colony-Stimulating Factor

Given subcutaneously

Intervention Type: BIOLOGICAL

Mitoxantrone

Given IV

Intervention Type: DRUG

Other Intervention Names

2-CdA; 2CDA; CdA; Cladribina; Leustat; Leustatin; Leustatine; RWJ-26251; .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; Recombinant Colony-Stimulating Factor 3; rhG-CSF; 143011-72-7; Dihydroxyanthracenedione; Mitozantrone

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, 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary-Beth Percival, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2019-07696

Identifier Type: REGISTRY

Identifier Source: secondary_id

RG1005551

Identifier Type: OTHER

Identifier Source: secondary_id

10310

Identifier Type: OTHER

Identifier Source: secondary_id

RG1005551

Identifier Type: -

Identifier Source: org_study_id