Clinical Trials /

Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia

NCT03760523

Description:

This study is to determine the safety and recommended dosing of Minnelide in Acute Myeloid Leukemia (AML)

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia
  • Official Title: Phase 1/1b Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: MCC-19742
  • NCT ID: NCT03760523

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
MinnelideMinnelide Dose Escalation

Purpose

This study is to determine the safety and recommended dosing of Minnelide in Acute Myeloid Leukemia (AML)

Detailed Description

      This phase 1 dose escalation clinical trial will establish the maximum tolerated dose (MTD)
      and recommended phase 2 dose (RP2D) of Minnelide as single-agent in relapsed/refractory (R/R)
      acute myeloid leukemia (AML) patients who are ineligible to receive intensive chemotherapy.
      The oral formulation of Minnelide will be used. Minnelide is a prodrug of triptolide (a
      potent heat shock protein (HSP) 70 inhibitor) with promising preclinical activity in AML.
    

Trial Arms

NameTypeDescriptionInterventions
Minnelide Dose EscalationExperimentalA 3+3 design will be used. The first 3 patients will be treated at dose level 1. If none experience a Dose Limiting Toxicity (DLT), the next 3 patients will be treated at dose level 2. If a DLT is observed in 1 out of 3 patients at dose level 1, up to an 3 more patients will be enrolled and treated at that dose level. If 2 patients at dose level have DLTs, dosing will be lowered to dose level -1 (.5 mg daily, taken orally). If 2 or more of the up to 6 patients at any dose level have DLTs, the preceding dose will be declared the Maximum Tolerated Dose (MTD). If more than 1 DLT occurs at Dose Level -1, the investigators will consider stopping the study. Once the MTD has been established, an additional 10 patients will be enrolled at this level to better characterize safety and tolerability.
  • Minnelide

Eligibility Criteria

        Inclusion Criteria:

          -  Adults ages 18 years or older.

          -  Participant must have relapsed or refractory acute myeloid leukemia (AML) (excluding
             acute promyelocytic leukemia).

          -  Relapsed patients must have received at least 1 induction chemotherapy regimen or two
             cycles of a hypomethylating agent and achieved a Complete Response (CR), followed by
             relapse of disease.

          -  Refractory patients must have received at least 1 induction chemotherapy regimen or
             two cycles of hypomethylating agent without achieving a CR.

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

          -  Participants must have acceptable organ function.

          -  Be able and willing to adhere to the study visit schedule and other protocol
             requirements.

          -  Must be able to swallow capsules and have no evidence of GI tract abnormality that
             would alter the absorption of oral medications.

          -  The effects of Minnelide on the developing human fetus are unknown. For this reason,
             women of child-bearing potential must have a negative serum or urine pregnancy test
             within 24 hours prior to beginning study treatment.

          -  Participants of childbearing potential must practice contraception. Females of
             childbearing potential: Recommendation is for 2 effective contraceptive methods during
             the study. Male participants with female partners who are of childbearing potential:
             Recommendation is for male and partner to use at least 2 effective contraceptive
             methods, as described above, during the study. Should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately.

          -  Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with Minnelide, breastfeeding mothers must agree
             to discontinue nursing if the mother is treated with Minnelide.

          -  Provision of signed and dated informed consent document

          -  Patients with prior allogeneic stem cell transplant who experience relapse of AML are
             eligible if they are off of immunosuppressive therapy and without any evidence of
             graft-versus-host disease (GVHD)

        Exclusion Criteria:

          -  Participants may not have received any therapy with any investigational products,
             systemic anti-neoplastic therapy, or radiotherapy within 14 days prior to Cycle 1 Day
             1. Patients actively receiving hydroxyurea are eligible and may continue to receive
             hydroxyurea during protocol treatment.

          -  Candidates for standard and/or potentially curative treatments.

          -  Major surgery within 28 days prior to Cycle 1 Day 1.

          -  New York Heart Association Class III or IV heart failure, myocardial infarction within
             the past 6 months, unstable arrhythmia, or evidence of ischemia on an
             electrocardiogram (EKG)

          -  Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy

          -  Known, active HIV, Hepatitis A, B or C infection (prior Hepatitis C infection that has
             been treated and determined to be cured is allowed)

          -  Symptomatic central nervous system (CNS) involvement with leukemia

          -  A concurrent second active and non-stable malignancy with the exception of
             non-melanoma skin cancer or carcinoma in-situ.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of Minnelide
Time Frame:Up to 28 days for each dosing cohort
Safety Issue:
Description:MTD will be determined by testing increasing doses up to 1.25 mg daily. MTD reflects highest dose of drug that did not cause a Dose Limiting Toxicity (DLT).

Secondary Outcome Measures

Measure:Complete Response (CR)
Time Frame:Up to 12 months
Safety Issue:
Description:Participants who experience Complete Response (CR) and Complete Response with Incomplete Blood Count Recovery (CRi) rate as defined by 2003 International Working Group (IWG) for AML.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 12 months
Safety Issue:
Description:Overall Response Rate is defined as CR + CRi + partial response (PR) as defined by 2003 IWG criteria for AML.
Measure:Relapse Free Survival (RFS)
Time Frame:Up to 18 months
Safety Issue:
Description:RFS is defined as time interval between achievement of CR to time of relapse.
Measure:Overall Survival (OS)
Time Frame:Up to 12 months
Safety Issue:
Description:OS defined as time interval from time of enrollment onto the clinical trial to death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • leukemia
  • myeloid leukemia

Last Updated

February 5, 2020