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

Primary Purpose

Myeloid Neoplasm, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cladribine

Cytarabine

Recombinant Granulocyte Colony-Stimulating Factor

Mitoxantrone

About this trial

This is an interventional treatment trial for Myeloid Neoplasm focused on measuring Myeloid and Monocytic Leukemia, Other Hematopoietic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (CI-CLAM, G-CSF)

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Treatment responses

Will assess treatment responses (e.g. complete response [CR] +/- minimal residual disease [MRD] , incomplete CR, morphologic leukemia free state, partial response, resistant disease).

Incidence of adverse events

Will use the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for toxicity and adverse event reporting.

Full Information

NCT ID

NCT04196010

First Posted

December 10, 2019

Last Updated

January 5, 2022

Sponsor

University of Washington

1. Study Identification

Unique Protocol Identification Number

NCT04196010

Brief Title

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

Official Title

Dose-Finding (Phase 1) Study of Continuous Infusion Cladribine, Cytarabine and Mitoxantrone (CI-CLAM) for Adults With Relapsed/Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms Treated at UW/SCCA

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Terminated

Why Stopped

Terminated due to unfavorable risk-benefit ratio of investigational regimen.

Study Start Date

May 8, 2020 (Actual)

Primary Completion Date

October 13, 2021 (Actual)

Study Completion Date

October 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Washington

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myeloid Neoplasm, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

Keywords

Myeloid and Monocytic Leukemia, Other Hematopoietic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (CI-CLAM, G-CSF)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cladribine

Other Intervention Name(s)

2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Other Intervention Name(s)

.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

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

Recombinant Granulocyte Colony-Stimulating Factor

Other Intervention Name(s)

Recombinant Colony-Stimulating Factor 3, rhG-CSF, 143011-72-7

Intervention Description

Given subcutaneously

Intervention Type

Drug

Intervention Name(s)

Mitoxantrone

Other Intervention Name(s)

Dihydroxyanthracenedione, Mitozantrone

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD)

Description

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

Time Frame

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 Outcome Measure Information:

Title

Treatment responses

Description

Will assess treatment responses (e.g. complete response [CR] +/- minimal residual disease [MRD] , incomplete CR, morphologic leukemia free state, partial response, resistant disease).

Time Frame

Up to 5 years post treatment

Title

Incidence of adverse events

Description

Will use the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for toxicity and adverse event reporting.

Time Frame

Up to 5 years post treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mary-Beth Percival, MD

Organizational Affiliation

Fred Hutch/University of Washington Cancer Consortium

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fred Hutch/University of Washington Cancer Consortium

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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