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

NCT04848974 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2020-0988NCI-2021-02298
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to two courses of Induction therapy, each course is approximately 4 weeks +/- 7 days

Secondary Outcomes (10)

• Number of Participants With a Response

  Up to 3 years, 4 months and 14 days

• Number of Participants With Complete Response (CR)

  Up to 3 years, 4 months and 14 days

• Number of Participants With Complete Remission Without Blood Count Recovery (CRi)

  Up to 3 years, 4 months and 14 days

• Number of Participants to Reach Morphologic Leukemia-free State (MLFS)

  Up to 3 years, 4 months and 14 days

• Number of Minimal Residual Disease (MRD) Negativity in Responders

  Up to 3 years, 4 months and 14 days

Study Arms (3)

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.

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.

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.

Drug: Cladribine; Drug: Cytarabine; Drug: Uproleselan

Interventions

Cladribine DRUG

Given IV

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

Ph 1 Treatment Dose Level -1 Cladaribine 3.75mg/m^2; Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2; Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2

Cytarabine DRUG

Given SC

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

Ph 1 Treatment Dose Level -1 Cladaribine 3.75mg/m^2; Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2; Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2

Uproleselan DRUG

Given IV

Also known as: GMI-1271

Ph 1 Treatment Dose Level -1 Cladaribine 3.75mg/m^2; Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2; Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2

Eligibility Criteria

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

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

Cladribine; Cytarabine; uproleselan

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

Results Point of Contact

• Title: Tapan Kadia MD/Professor
• Organization: The University of Texas MD Anderson Cancer Center

tkadia@mdanderson.org

713-563-3534

Study Officials

• Tapan M Kadia

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 19, 2021
• Study Start: June 11, 2021
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: October 20, 2025
• Results First Posted: October 20, 2025

Record last verified: 2025-10

Locations

US (1)