Trial Outcomes & Findings for Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia (NCT NCT04848974)

Last Updated: 2025-10-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

37 participants

Primary outcome timeframe

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

Results posted on

2025-10-20

Participant Flow

Participant milestones

Participant milestones
Measure	Ph 1 Treatment Dose Level -1 Cladaribine 3.75mg/m^2 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Overall Study STARTED	3	9	25
Overall Study COMPLETED	3	9	25
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ph 1 Treatment Dose Level -1 Cladaribine 3.75mg/m^2 n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants	32 Participants n=4 Participants
Age, Continuous	76 years n=5 Participants	68 years n=7 Participants	73 years n=5 Participants	73 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	19 Participants n=5 Participants	24 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	6 Participants n=7 Participants	24 Participants n=5 Participants	33 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	3 participants n=5 Participants	9 participants n=7 Participants	25 participants n=5 Participants	37 participants n=4 Participants

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=12 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Recommended Phase II Dose	5 mg/m^2	—	—

SECONDARY outcome

Timeframe: Up to 3 years, 4 months and 14 days

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.

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Number of Participants With a Response	1 Participants	4 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to 3 years, 4 months and 14 days

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.

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Number of Participants With Complete Response (CR)	0 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 3 years, 4 months and 14 days

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).

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Number of Participants With Complete Remission Without Blood Count Recovery (CRi)	0 Participants	1 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 3 years, 4 months and 14 days

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.

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Number of Participants to Reach Morphologic Leukemia-free State (MLFS)	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 3 years, 4 months and 14 days

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).

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=1 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=4 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=7 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Number of Minimal Residual Disease (MRD) Negativity in Responders	1 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days

Time from date of treatment start until date of death due to any cause.

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Overall Survival	0.8 Months Interval 0.6 to 4.8	5.5 Months Interval 1.7 to 26.3	3.8 Months Interval 0.4 to 12.7

SECONDARY outcome

Timeframe: From date of CR/CRi to date of disease relapse, death or last follow-up, whichever occurred first, assessed up to 4.5 years

The date of Complete Response to the date of loss of response or last follow-up.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment start to date of death, relapse or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days

Time from date of treatment start until the date of failure or death from any cause.

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Event-free Survival	0.6 Months Interval 0.5 to 2.8	3.1 Months Interval 0.7 to 26.3	1.7 Months Interval 0.4 to 7.2

SECONDARY outcome

Timeframe: Up to 3 years, 4 months and 14 days

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.

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=1 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=2 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=5 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
The Number of Participants With Complete Cytogenetic Response (CCyR)	1 Participants	1 Participants	2 Participants

SECONDARY outcome

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

Number of participants who died during the induction period of therapy.

Outcome measures

Outcome measures
Measure	All Participants Enrolled in Phase 1b n=3 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 Participants 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
Induction Mortality, Number of Participants	0 Participants	0 Participants	4 Participants

Adverse Events

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

Serious events: 3 serious events

Other events: 3 other events

Deaths: 3 deaths

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

Serious events: 3 serious events

Other events: 6 other events

Deaths: 7 deaths

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

Serious events: 15 serious events

Other events: 22 other events

Deaths: 24 deaths

Serious adverse events

Other adverse events

Additional Information

Tapan Kadia MD/Professor

The University of Texas MD Anderson Cancer Center

Phone: 713-563-3534

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ph 1 Treatment Dose Level -1 Cladaribine 3.75mg/m^2 n=3 participants at risk 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 1 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=9 participants at risk 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV	Ph 2 Treatment Dose Level 1 Cladaribine 5 mg/m^2 n=25 participants at risk 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. Cladribine: Given IV Cytarabine: Given SC Uproleselan: Given IV
General disorders Chills	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	6.7% 1/15 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	6.7% 1/15 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	11.1% 1/9 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/15 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	4.0% 1/25 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	11.1% 1/9 • Number of events 2 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	12.0% 3/25 • Number of events 4 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
General disorders General disorders and administration site conditions - Other, specify	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	4.0% 1/25 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Vascular disorders Hypotension	33.3% 1/3 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/25 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Nervous system disorders Intracranial hemorrhage	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	4.0% 1/25 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Infections and infestations Lung infection	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	16.0% 4/25 • Number of events 4 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
General disorders Non-cardiac chest pain	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	4.0% 1/25 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	11.1% 1/9 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/25 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Gastrointestinal disorders Rectal pain	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	4.0% 1/25 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	8.0% 2/25 • Number of events 2 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Nervous system disorders Seizure	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/9 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	4.0% 1/25 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Infections and infestations Sepsis	66.7% 2/3 • Number of events 2 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	11.1% 1/9 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	12.0% 3/25 • Number of events 3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Infections and infestations Sinusitis	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	11.1% 1/9 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/25 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days
Nervous system disorders Stroke	0.00% 0/3 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	11.1% 1/9 • Number of events 1 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days	0.00% 0/25 • From treatment start to the date of death or last follow-up, whichever occurred first, Up to 3 years, 4 months and 14 days