Secondary Acute Myeloid LeukemiaPhase 1/2NCT04848974

Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia

A Phase 1/2 study testing Cladribine, Cytarabine and Uproleselan in people with Secondary Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Secondary Acute Myeloid Leukemia
What is being tested?: Cladribine, Cytarabine and Uproleselan
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 1 siteUnited States
Study dates: 11 Jun 2021to 30 Oct 2024
Phase: Phase 1/2

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

Patients with a diagnosis of treated secondary-AML (TS-AML) who have not received therapy for their AML will be eligible.
TS-AML is defined as AML arising from a previously treated antecedent myeloid neoplasm (myelodysplastic syndrome or myeloproliferative neoplasm that has been previously treated with hypomethylating agents).
Patients must be at least 7 days from their last therapy for the antecedent myeloid neoplasm
Age >/= 18 years.
Adequate organ function as defined below:
liver function (total bilirubin < 2mg/dL, AST and/or ALT <3 x ULN - or <5 x ULN if related to leukemic involvement)

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kidney function (creatinine < 1.5 x ULN ).
known cardiac ejection fraction of > or = 45% within the past 6 months
ECOG performance status of ≤ 2.
A negative urine or serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
Patient must have the ability to understand the requirements of the study and informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.

Who cannot join

Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients with documented hypersensitivity to any of the components of the chemotherapy program.
Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
Prior treatment with uproleselan.
Patients with a diagnosis of acute promyelocytic leukemia (AML-M3) will be excluded from this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

M D Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase Ib/II Study of Uproleselan Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Uproleselan Plus Cladribine Plus LDAC in Patients With Treated Secondary AML (TS-AML)

This phase Ib/II trial finds out the best dose and effect of cladribine and low dose cytarabine when given in combination with uproleselan in treating patients with treated secondary acute myeloid leukemia. Chemotherapy drugs, such as uproleselan, cladribine, and low dose cytarabine, 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.

Read the detailed description

PRIMARY OBJECTIVE:

To determine the safety, tolerability, and recommended phase II dose (RP2D) of uproleselan combined with cladribine + low dose cytarabine (LDAC) in patients with treated-secondary acute myeloid leukemia (AML) (ts-AML).

SECONDARY OBJECTIVES:

To assess the efficacy (overall response rate [ORR], complete response [CR], complete response without blood count recovery [CRi], CR with partial hematologic recovery [CRh], partial response [PR], or morphologic leukemia-free state of uproleselan combined with cladribine + LDAC in patients with ts-AML.

II. To assess the rate of minimal residual disease (MRD) negativity by flow cytometry at response.

III. To assess overall survival (OS), remission duration (CRd), and progression-free survival (PFS) in patients with ts-AML treated with uproleselan combined with cladribine + LDAC.

IV. To assess the rate of complete cytogenetic response (CCyR) in patients with ts-AML with abnormal baseline karyotype, treated with uproleselan combined with cladribine + LDAC.

To assess toxicity and induction mortality of patients with AML treated with uproleselan added to cladribine + LDAC.

EXPLORATORY OBJECTIVES:

To explore biomarkers of response and resistance in patients with ts-AML treated with uproleselan combined with cladribine + LDAC.

II. To examine the correlation of E-selectin ligand-forming glycosylation genes of leukemic blasts with clinical outcome.

OUTLINE: This is a phase I, dose-escalation study of cladribine and cytarabine followed by a phase II study.

INDUCTION THERAPY: Patients receive uproleselan intravenously (IV) over 20 minutes on day 1 and every (Q) 12 hours on days 2-12, cladribine IV over 1-2 hours on days 1-5 and cytarabine subcutaneously (SC) twice daily (BID) on days 1-10 in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a second induction cycle.

CONSOLIDATION/MAINTENANCE THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q12 hours on days 2-1. Patients who have achieved at least CR/CRi or morphologic leukemia-free state after induction therapy receive uproleselan IV once daily (QD) on days 1-12. Patients also receive cladribine IV over 1-2 hours on days 1-3 and cytarabine SC BID on days 1-10. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

Conditions: Secondary Acute Myeloid Leukemia
Being tested: Cladribine, Cytarabine, Uproleselan

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 SC
UproleselanDrug
Also called GMI-1271
Given IV

Study groups in NCT04848974
Study group	Role	What they receive
Ph 1 Treatment Dose Level -1 Cladaribine 3.75mg/m^2	Experimental	INDUCTION THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q 12 hours on days 2-12, cladribine IV over 1-2 hours on days 1-5 and cytarabine SC BID on days 1-10 in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a second induction cycle. CONSOLIDATION/MAINTENANCE THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q12 hours on days 2-1. Patients who have achieved at least CR/CRi or morphologic leukemia-free state after induction therapy receive uproleselan IV QD on days 1-12. Patients also receive cladribine IV over 1-2 hours on days 1-3 and cytarabine SC BID on days 1-10. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Uproleselan
Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2	Experimental	INDUCTION THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q 12 hours on days 2-12, cladribine IV over 1-2 hours on days 1-5 and cytarabine SC BID on days 1-10 in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a second induction cycle. CONSOLIDATION/MAINTENANCE THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q12 hours on days 2-1. Patients who have achieved at least CR/CRi or morphologic leukemia-free state after induction therapy receive uproleselan IV QD on days 1-12. Patients also receive cladribine IV over 1-2 hours on days 1-3 and cytarabine SC BID on days 1-10. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Uproleselan
Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2	Experimental	INDUCTION THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q 12 hours on days 2-12, cladribine IV over 1-2 hours on days 1-5 and cytarabine SC BID on days 1-10 in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a second induction cycle. CONSOLIDATION/MAINTENANCE THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q12 hours on days 2-1. Patients who have achieved at least CR/CRi or morphologic leukemia-free state after induction therapy receive uproleselan IV QD on days 1-12. Patients also receive cladribine IV over 1-2 hours on days 1-3 and cytarabine SC BID on days 1-10. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Uproleselan

What is being measured

The primary outcome is the main question the study is designed to answer.

Recommended Phase II Dose
During safety lead-in, we will use the Bayesian optimal interval (BOIN) design to identify the RP2D of the combination therapy. If the observed DLT rate at the current dose is . 0.236, escalate the dose to the next higher dose level;
. if the observed DLT rate at the current dose is . 0.359, de-escalate the dose to the next lower dose level; otherwise, stay at the current dose.
Measured: Up to two courses of Induction therapy, each course is approximately 4 weeks +/- 7 days

Secondary outcomes (9)

Number of Participants With a Response
Response is Complete Remission (CR) + Complete Remission Without Count Recovery (CRi) + Morphologic Leukemia-Free State (MLFS) - CR is Disappearance of all clinical and/or radiologic evidence of disease, including extramedullary leukemia. Neutrophil count . 1.0 x 10^9/L and platelet count . 100 x 10^9/L, and bone marrow differential showing . 5% blasts. CRi is Have met all criteria for CR, except for either residual neutropenia (ANC < 1.0 x 10^9/L) or thrombocytopenia (platelet count < 100 x 10^9/L). MLFS is Bone marrow differential showing < 5% blasts, no evidence of peripheral blasts or extramedullary disease, but without peripheral blood count recovery to neutrophil count . 1.0 x 10^9/L \& platelet count . 100 x 10^9/L.
Measured: Up to 3 years, 4 months and 14 days
Number of Participants With Complete Response (CR)
Disappearance of all clinical and/or radiologic evidence of disease, including extramedullary leukemia. Neutrophil count . 1.0 x 10^9/L and platelet count . 100 x 10^9/L, and bone marrow differential showing . 5% blasts.
Measured: Up to 3 years, 4 months and 14 days
Number of Participants With Complete Remission Without Blood Count Recovery (CRi)
Have met all criteria for CR, except for either residual neutropenia (ANC < 1.0 x 10^9/L) or thrombocytopenia (platelet count < 100 x 10^9/L).
Measured: Up to 3 years, 4 months and 14 days
Number of Participants to Reach Morphologic Leukemia-free State (MLFS)
Bone marrow differential showing < 5% blasts, no evidence of peripheral blasts or extramedullary disease, but without peripheral blood count recovery to neutrophil count . 1.0 x 10^9/L \& platelet count . 100 x 10^9/L.
Measured: Up to 3 years, 4 months and 14 days
Number of Minimal Residual Disease (MRD) Negativity in Responders
Measures the Minimal Residual Disease (MRD) negativity in participants who achieve Complete Remission (CR) or Complete remission without count recovery (CRi) - CR is Disappearance of all clinical and/or radiologic evidence of disease, including extramedullary leukemia. Neutrophil count . 1.0 x 10^9/L and platelet count . 100 x 10^9/L, and bone marrow differential showing . 5% blasts. CRi is Have met all criteria for CR, except for either residual neutropenia (ANC < 1.0 x 10^9/L) or thrombocytopenia (platelet count < 100 x 10^9/L).
Measured: Up to 3 years, 4 months and 14 days
Overall Survival
Time from date of treatment start until date of death due to any cause.
Measured: From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Event-free Survival
Time from date of treatment start until the date of failure or death from any cause.
Measured: From treatment start to date of death, relapse or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
The Number of Participants With Complete Cytogenetic Response (CCyR)
To assess the rate of complete cytogenetic response (CCyR) in patients with abnormal baseline karyotype, treated with uproleselan combined with cladribine + LDAC. Participants were evaluated for abnormal baseline karyotype and evaluated again after treatment.
Measured: Up to 3 years, 4 months and 14 days
Induction Mortality, Number of Participants
Number of participants who died during the induction period of therapy.
Measured: Up to two courses of Induction therapy, each course is approximately 4 weeks +/- 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Jun 202130 Oct 2024

First posted19 Apr 2021
Study start11 Jun 2021
Primary completion30 Oct 2024
Study completion30 Oct 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Secondary Acute Myeloid LeukemiaStudies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe 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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04848974
Sponsor's protocol ID: 2020-0988
Other IDs: NCI-2021-02298, 2020-0988
Status last verified: Oct 2025
First submitted: 5 Apr 2021
Last updated: 5 Jun 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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