Study of Uproleselan Administered with Chemotherapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Clinical Trial Title

A Phase III Randomized, Double-Blind Trial to Evaluate the Efficacy of Uproleselan Administered with Chemotherapy versus Chemotherapy Alone in Patients with Relapsed/Refractory Acute Myeloid Leukemia

National Clinical Trial Number:

NCT03616470

Contact Information

Cathleen Maidlow

Clinical Trial Protocol Description:

This research study is studying a medication, uproleselan (GMI-1271), in combination with standard chemotherapy as a possible treatment for this diagnosis. The study medication, uproleselan (GMI-1271), is experimental. That means the United States Food and Drug Administration (FDA) has not determined that it is safe and effective for any use, and has not approved it for use in humans. Uproleselan is being studied to treat different types of cancers found in the blood.

Clinical Trial Eligibility Criteria:

In order to participate you must meet the following criteria:

  • Are between 18 and 75 years of age.
  • Have AML diagnosed with ≥20% myeloid marrow blasts or peripheral blood blasts per WHO criteria at the time of initial diagnosis as per local documentation.
  • For subjects with primary refractory AML:
    • 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.
    • 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.
        • 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.
        • 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.
        • 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.
    • Relapse from first remission (CR, CRi, CRp, CRh) lasting <90 days:
      • After achieving first remission from any induction regimen, may have received consolidation before experiencing relapse.
  • For subjects with relapsed AML, must be in first or second untreated relapse:
    • Relapsed disease is defined as having ≥5% blasts in the bone marrow after having achieved previous CR, CRi, CRp, or CRh by ELN Response Criteria. Minimum allowable remission duration is ≥90 days for CR1 and ≥45 days for CR2. Isolated extramedullary disease is not allowed.
    • Cytotoxic or non-cytotoxic regimen used with the intent to induce remission, regardless of the agents used, will be counted as an induction attempt towards this assessment of untreated relapse. For example: anthracycline-based, cytarabine-based, clofarabine-based, cladribine-based, and antibody-drug conjugates.
    • Certain regimens (venetoclax/HMA, venetoclax/LDAC, single agent HMA) are allowed.
    • Single agent FLT3 inhibitors, tyrosine kinase inhibitors, IDH1/IDH2 inhibitors or similar targeted inhibitors are not considered cytotoxic chemotherapy for the purposes of this assessment and are allowed.
  • One prior HSCT is allowed.
  • Have not received the chemotherapy regimen to be used for induction on this trial.
    • For example, a subject who received MEC previously could receive FAI, but not MEC, on this trial.
  • Are considered medically eligible to receive the chemotherapy regimen to be used for induction on this trial.
  • Have 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.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Have an estimated life expectancy >4 weeks.
  • Have written informed consent provided in accordance with federal, local, and institutional guidelines.
  • Are willing and able to participate in all required evaluations and procedures in this trial protocol.

You will be excluded from the study if any of the following criteria apply to you:

  • Have acute promyelocytic leukemia.
  • Have acute leukemia of ambiguous lineage (biphenotypic leukemia).
  • Have chronic myeloid leukemia with myeloid blast crisis.
  • Have secondary refractory AML (e.g., treated for current relapse without achieving remission).
    • For clarity, cytotoxic or non-cytotoxic regimen used with the intent to induce remission, regardless of the agents used, will be counted as an induction attempt towards this assessment. For example: anthracycline-based, cytarabine-based, clofarabine-based, cladribine-based, and antibody-drug conjugates.
    • Certain regimens (venetoclax/HMA, venetoclax/LDAC, single agent HMA) are allowed.
    • Single agent FLT3 inhibitors, tyrosine kinase inhibitors, IDH1/IDH2 inhibitors or similar targeted inhibitors are not considered cytotoxic chemotherapy for the purposes of this assessment and are allowed.
  • Have prior enrollment in this clinical trial (GMI-1271-301).
  • Have active signs or symptoms of CNS involvement by malignancy (lumbar puncture not required). Prior history of CNS involvement is acceptable.
  • Have prior G-CSF, granulocyte macrophage-colony stimulating factor (GM-CSF) or plerixafor within 7 days of uproleselan/placebo dosing.
  • Have allogeneic HSCT ≤4 months, autologous HSCT ≤3 months or donor lymphocyte infusion (DLI) ≤6 weeks prior to uproleselan/placebo dosing.
  • Have acute graft versus host disease (GVHD) ≥Grade 2 or active chronic GVHD requiring immunosuppressive therapy. Graft versus host disease prophylaxis in the absence of chronic GVHD must be discontinued at least 14 days before uproleselan/placebo dosing.
  • Have had any immunotherapy or radiotherapy within 28 days of uproleselan/placebo dosing; any other experimental therapy or chemotherapy within 14 days of uproleselan/placebo dosing:
    • With the exception of hydroxyurea, which may be used to control peripheral blast count prior to uproleselan/placebo dosing.
    • With the exception of FLT3 inhibitors, TKI, or IDH1/IDH2 inhibitors, or similar targeted inhibitors, which are not considered cytotoxic chemotherapy. Such agents must be discontinued 5 days before uproleselan/placebo dosing.
  • Have abnormal liver function, as defined below. Confirm within 72 hours of randomization:
    • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ˃2.5x upper limit of normal (ULN) (at least one must be assessed, and any assessed must be within eligibility limit).
    • Direct bilirubin ˃2.0x ULN.
    • Unless due to underlying malignancy (document medical justification for this and confirm with medical monitor prior to randomization).
  • Have creatinine clearance <45 mL/min (Cockcroft-Gault method) or creatinine >1.5x ULN (any assessed must be within eligibility limit). Confirm within 72 hours of randomization.
  • Have known active infection with hepatitis A, B (e.g., HBsAg positive), or C (e.g., anti-HCV positive), or human immunodeficiency virus.
  • Have uncontrolled acute life-threatening bacterial, viral, or fungal infection.
  • Have had myocardial infarction within 6 months of uproleselan/placebo dosing, or subject has current significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hemodynamic instability, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
  • Have had major surgery within 4 weeks before uproleselan/placebo dosing.
  • Have previous or concurrent malignancy with the exception of:
    • Adequately treated basal or squamous cell carcinoma, in situ carcinoma of the cervix, or ductal carcinoma in situ of the breast.
    • Localized prostate cancer definitively treated with surgery or radiation; or stable on hormone therapy.
    • Other cancer from which the subject has been disease free for at least 2 years.
  • Have any medical, psychiatric, or other condition which, in the opinion of the investigator, unfavorably alters the risk-benefit of subject participation, is likely to interfere with trial completion, assessments, or interpretation of trial results, or otherwise would make the subject an inappropriate subject for this trial.
  • Are pregnant or nursing (lactating).
  • Are a woman of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during the trial and for 3 months after the last dose of uproleselan/placebo. Women who are postmenopausal with amenorrhea for at least 1 year prior to trial entry and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status (>28U/L) will be considered NOT of child-bearing potential. Highly effective contraception includes:
    • Total abstinence with a male partner.
    • Female sterilization (has had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before uproleselan/placebo. In case of oophorectomy alone, the subject would be eligible only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
    • Male sterilization (at least 6 months prior to Screening). For female subjects on the trial, the vasectomized male partner should be the sole partner for that subject.
    • BOTH of the following forms of contraception consistently used together:
      • Injected, transdermal, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%) with the exception of intrauterine devices, which are excluded due to the risk of infection and bleeding.
      • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with or without spermicidal foam/gel/film/cream/vaginal suppository.
  • Are a man who is sexually active and not willing to use condoms during the trial and for 3 months after the last dose of uproleselan/placebo, unless they have undergone vasectomy for sterilization (at least 6 months prior to Screening), are excluded from trial participation.

This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.

Study Details

Clinical Trial Investigator

Melissa Larson, MD

Contact Information

Cathleen Maidlow

Location

Rush University Medical Center

1620 W Harrison St
Chicago, IL 60612

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