Study to Evaluate the Efficacy of Uproleselan in Combination With Chemotherapy in Chinese Patients With R/R AML

Apollomics

Status and phase: Terminated; Phase 3

Conditions: Relapsed/Refractory AML

Treatments: Drug: Uproleselan; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05054543

APL-106-02

Details and patient eligibility

About

This bridging study will evaluate the efficacy of uproleselan, a specific E-selectin antagonist, in combination with chemotherapy to treat Chinese relapsed/refractory AML patients, compared to chemotherapy alone. The safety of uproleselan when given with chemotherapy will also be investigated in patients with relapsed/refractory AML

Full description

This trial will enroll approximately 140 randomized subjects 18 through 75 years of age at the time of randomization with primary refractory AML or relapsed AML (first or second untreated relapse) and eligible to receive induction chemotherapy as described.

Randomization will be done at trial entry at a 1:1 ratio, and will be stratified by age (<60, ≥60 years) and disease status (primary refractory/early relapse ≤6 months, late relapse>6 months) and prior HSCT status. Treatment assignment received at randomization will be maintained during all induction and consolidation cycles.

This trial will have the following sequential phases: screening, baseline, induction treatment and count recovery, response assessment, consolidation treatment (if remission is achieved), and follow-up for relapse and survival assessment. Subjects not achieving remission will continue to be followed for long-term trial endpoints such as disease progression and survival. Blinding will be maintained until database lock. This study will carry out long-term follow-up for all subjects for a maximum of 3 years or death of subjects or withdrawal of consent.

Enrollment: 140 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ≥18 years and ≤75 years in age

2. AML diagnosed with ≥20% myeloid marrow blasts or peripheral blood blasts per WHO criteria(2008) at the time of initial diagnosis

3. For subjects with primary refractory AML:

   1. Refractory disease is defined as persistent disease (≥5% blasts in the bone marrow) at least 28 days after initiation of anthracycline-containing induction therapy or relapse from a first remission (CR, CRi, complete remission with incomplete platelet recovery [CRp], CRh) lasting for <90 days. Isolated extramedullary disease is not allowed.

   2. Persistent disease (≥5% blasts in the bone marrow): Must have received 1 (and only 1) prior anthracycline-containing induction regimen. Except as defined below, a second induction with intent to induce remission is not allowed.

      1. Re-induction within 28 days with a comparable regimen containing the same chemotherapy agents (e.g., cytarabine/daunorubicin '7+3' and '5+2'; or cytarabine/daunorubicin '7+3' and '7+3') is allowed.
      2. Re-induction within 28 days with a comparable regimen using an alternative anthracycline (e.g., cytarabine/daunorubicin in the first induction and cytarabine/idarubicin in the second) is allowed.
      3. Previous induction with certain regimens (venetoclax/hypomethylating agent [HMA], venetoclax/LDAC, single agent HMA) followed by an anthracycline induction regimen is allowed. May have achieved remission with certain regimens (venetoclax/HMA, venetoclax/LDAC, single agent HMA) and then experience relapse now refractory to anthracycline-containing induction.

   3. Relapse from first remission (CR, CRi, CRp, CRh) lasting <90 days: 1) After achieving first remission from any induction regimen, may have received consolidation before experiencing relapse.

4. No more than one prior stem cell transplant.

5. Has not received the chemotherapy regimen to be used for induction on this trial.

6. Is considered medically eligible to receive the chemotherapy regimen to be used for induction on this trial.

7. Peripheral absolute blast count (ABC) ≤40.0 x 109/L (ABC = total white blood cells [WBC] x blast % in peripheral blood). Hydroxyurea to control absolute blast count is allowed prior to uproleselan/placebo dosing.

8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion criteria

1. Patients with acute promyelocytic leukemia
2. Acute leukemia of ambiguous lineage (biphenotypic leukemia)
3. Chronic myeloid leukemia with myeloid blast crisis
4. Active signs or symptoms of CNS involvement by malignancy (No lumbar puncture required)
5. Prior use of G-CSF, CM-CSF or plerixafor within 7 days of dosing.
6. Allogeneic HSCT ≤ 4 months, autologous HSCT ≤ 3 months or donor lymphocyte infusion (DLI) ≤ 6 weeks prior to Uproleselan/placebo dosing.
7. Any immunotherapy or radiotherapy therapy within 28 days of dosing; any other experimental therapy or chemotherapy within 14 days of dosing
8. Inadequate organ function.
9. Abnormal liver function.
10. Known active infection with hepatitis A, B, or C, or human immunodeficiency virus.
11. Creatinine clearance <45 mL/min (Cockcroft-Gault method) or creatinine >1.5x ULN (any assessed must be within eligibility limit).
12. Uncontrolled acute life-threatening bacterial, viral, or fungal infection.
13. Myocardial infarction within 6 months of uproleselan/placebo dosing, or subject has current significant cardiovascular disease.
14. Major surgery within 4 weeks before uproleselan/placebo dosing.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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140 participants in 2 patient groups, including a placebo group

Uproleselan

Experimental group

Description:

Uproleselan in combination with mitoxantrone, etoposide and cytarabine (MEC) during induction; Uproleselan in combination with HiDAC/IDAC during consolidation

Treatment:

Drug: Uproleselan

Placebo (Saline, 0.9% Sodium Chloride)

Placebo Comparator group

Description:

Placebo in combination with mitoxantrone, etoposide and cytarabine (MEC) during induction; Placebo in combination with HiDAC/IDAC during consolidation

Treatment:

Drug: Placebo