Myeloid NeoplasmPhase 1NCT04196010
Continuous Infusion Chemotherapy (CI-CLAM) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms
A Phase 1 study testing Cladribine, Cytarabine and Recombinant Granulocyte Colony-Stimulating Factor in people with Myeloid Neoplasm and Recurrent Acute Myeloid Leukemia, run by University of Washington at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloid Neoplasm, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- What is being tested?
- Cladribine, Cytarabine and Recombinant Granulocyte Colony-Stimulating Factor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2020to 13 Oct 2021
- 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
- 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)
Show all 10Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
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
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.
Read the 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.
- Being tested
- Cladribine, Cytarabine, Recombinant Granulocyte Colony-Stimulating Factor, Mitoxantrone
- Keywords
- Myeloid and Monocytic Leukemia, Other Hematopoietic
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Monocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called 2-CdA, 2CDA, CdA, Cladribina
Given IV
CytarabineDrug
Also called .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
Given IV
Recombinant Granulocyte Colony-Stimulating FactorBiological
Also called Recombinant Colony-Stimulating Factor 3, rhG-CSF, 143011-72-7
Given subcutaneously
MitoxantroneDrug
Also called Dihydroxyanthracenedione, Mitozantrone
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cladribine; Drug: Cytarabine; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Drug: Mitoxantrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Will assess treatment responses (e.g. complete response [CR] +/- minimal residual disease [MRD] , incomplete CR, morphologic leukemia free state, partial response, resistant disease).
Measured: Up to 5 years post treatment
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.
Measured: Up to 5 years post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2019
- Study start8 May 2020
- Primary completion13 Oct 2021
- Study completion13 Oct 2021
Why it stopped: Terminated due to unfavorable risk-benefit ratio of investigational regimen.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myeloid NeoplasmStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mary-Beth Percival, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04196010
- Sponsor's protocol ID
- RG1005551
- Other IDs
- NCI-2019-07696, RG1005551, 10310
- Status last verified
- Jan 2022
- First submitted
- 10 Dec 2019
- Last updated
- 28 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04196010
- Acronym / sponsor ID
- RG1005551
- Keywords
- Myeloid and Monocytic Leukemia, Other Hematopoietic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to unfavorable risk-benefit ratio of investigational regimen.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Study start
- 8 May 2020 (actual)
- Primary completion
- 13 Oct 2021 (actual)
- Study completion
- 13 Oct 2021 (actual)
- First posted
- 12 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CI-CLAM, G-CSF) | Experimental | Drug: Cladribine, Drug: Cytarabine, Biological: Recombinant Granulocyte Colony-Stimulating Factor, Drug: MitoxantronePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineAlso: 2-CdA, 2CDA, CdA, CladribinaGiven IV | Drug | Treatment (CI-CLAM, G-CSF) |
| CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IV | Drug | Treatment (CI-CLAM, G-CSF) |
| Recombinant Granulocyte Colony-Stimulating FactorAlso: Recombinant Colony-Stimulating Factor 3, rhG-CSF, 143011-72-7Given subcutaneously | Biological | Treatment (CI-CLAM, G-CSF) |
| MitoxantroneAlso: Dihydroxyanthracenedione, MitozantroneGiven IV | Drug | Treatment (CI-CLAM, G-CSF) |
Primary outcome
Maximum tolerated dose (MTD)
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)
Will use the Bayesian Optimal Interval ("BOIN") design to select the MTDs for continuous infusion G-CSF, cladribine, cytarabine and mitoxantrone (CI GCLAM).
2 secondary outcomes
Treatment responses
Time frame: Up to 5 years post treatment
Incidence of adverse events
Time frame: Up to 5 years post treatment
Results and safety
The study was stopped early (reason given: Terminated due to unfavorable risk-benefit ratio of investigational regimen.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2023.
- Individual participant dataSharing planned: No
Related trials for Myeloid Neoplasm
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary-Beth Percival, MD principal investigator
Fred Hutch/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cladribine, Cytarabine and Recombinant Granulocyte Colony-Stimulating Factor in people with Myeloid Neoplasm and Recurrent Acute Myeloid Leukemia, run by University of Washington 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 10 inclusion and 0 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: stopped early, as of the sponsor's last update on 28 Dec 2023. 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 was stopped early (reason given: Terminated due to unfavorable risk-benefit ratio of investigational regimen.). Results are not available in the source record.
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?
Maximum tolerated dose (MTD) (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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Dec 2023.