Clinical Trials /

Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd Salvage

NCT03926624

Description:

Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with AML relapsed/refractory after 2 or 3 prior induction regimens: Experimental arm: DFP-10917 14-day continuous intravenous (IV) infusion at a dose of 6 mg/m²/day followed by a 14-day resting period per 28-day cycles. Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine) or Intensive Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's prior induction treatment.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd Salvage
  • Official Title: Phase 3 Randomized Trial of DFP-10917 vs Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine) or Intensive Reinduction (High & Intermediate Dose Cytarabine Regimens) for Acute Myelogenous Leukemia Patients in Second or Third Salvage

Clinical Trial IDs

  • ORG STUDY ID: D18-11141
  • NCT ID: NCT03926624

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
DFP-10917Experimental
CytarabineControl
AzacitidineControl
DecitabineControl
MitoxantroneControl
EtoposideControl
FludarabineControl
IdarubicinControl

Purpose

Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with AML relapsed/refractory after 2 or 3 prior induction regimens: Experimental arm: DFP-10917 14-day continuous intravenous (IV) infusion at a dose of 6 mg/m²/day followed by a 14-day resting period per 28-day cycles. Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine) or Intensive Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's prior induction treatment.

Detailed Description

      Study to compare the rate of complete response (CR) and duration of CR, in patients with
      relapsed or refractory AML to two or three prior induction regimens that may have included
      intensive chemotherapy (e.g., "7+3" cytarabine and daunorubicin), epigenetic therapy (i.e.,
      azacitidine or decitabine), or targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal
      antibody), who will receive DFP-10917 versus non-intensive reinduction (LoDAC, azacitidine,
      decitabine) or intensive reinduction (high and intermediate dose cytarabine regimens) as a
      second or third salvage treatment.

      Experimental Arm DFP-10917 Dose: 6 mg/m²/day administered by continuous infusion for 14 days
      followed by a 14-day resting period per 28-day treatment cycle. If a patient experiences a
      significant treatment-related AE, the patient may undergo one dose reduction of DFP-10917 to
      4 mg/m²/day x 14 days for subsequent treatment cycles

      Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine) or Intensive
      Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's
      prior induction treatment. Control treatment is to be selected only from among the following.
      Institutional practice for administering these treatments are permitted, but the dose and
      days of drug administration should be followed as below.

      Non-Intensive Reinduction:

        -  LoDAC: 20 mg Cytarabine administered by subcutaneous (SC) injection, twice daily (BID)
           for 10 days, plus best supportive care per 28-day treatment cycle

        -  Azacitidine: 75 mg/m²/day administered by SC for 7 consecutive days (or 5+2), plus best
           supportive care per 28-day treatment cycle

        -  Decitabine: administered as continuous intravenous (CIV) infusion 20 mg/m² x 5 days plus
           best supportive care per 28 day treatment cycle

      Intensive Reinduction:

        -  High DAC = cytarabine at doses of 1-2 g/m²/day for up to 5 days, with a maximum total
           dose 10 g/m² per course

        -  FLAG = Days 1-5: fludarabine 30 mg/m² IV over 30 minutes, Days 1-5: cytarabine 1 2
           grm/m² over 4 hours daily x 5, and granulocyte colony-stimulating factor 5 mcg/kg or 300
           mcg/m² until Polymorphonuclear Neutrophil (PMN) recovery, with or without idarubicin
           Days 1-3 at 8 mg/m² IV daily x 3 (FLAG-Ida)

        -  MEC = Days 1-6: mitoxantrone 6 mg/m² IV bolus, etoposide 80 mg/m² IV over 1 hour, and
           cytarabine 1 grm/m² IV over 6 hrs

        -  Intermediate DAC = cytarabine 20 mg/m² IV daily x 5

      The selection of control arm treatment will be determined by the investigator depending on
      the patient's prior initial induction and salvage treatment regimen(s), as well as the
      patient's clinical condition and comorbidities. The investigator will select the patient's
      control treatment from among the non-intensive or intensive regimens prior to study treatment
      randomization in order to balance treatment allocation between the experimental and control
      treatment arms.
    

Trial Arms

NameTypeDescriptionInterventions
ExperimentalExperimentalDFP-10917 Dose: 6 mg/m²/day administered by continuous infusion for 14 days followed by a 14-day resting period per 28-day treatment cycle. If a patient experiences a significant treatment-related AE, the patient may undergo one dose reduction of DFP-10917 to 4 mg/m²/day x 14 days for subsequent treatment cycles
  • DFP-10917
ControlActive ComparatorNon-Intensive or Intensive Reinduction Non-Intensive: LoDAC: 20 mg Cytarabine SC injection BID 10days + best supportive care per 28day cycle Azacitidine: 75 mg/m²/day SC 7 days (or 5+2) + best supportive care per 28day cycle Decitabine: CIV 20 mg/m² x 5 days + best supportive care per 28day cycle Intensive: High DAC: cytarabine doses 1-2 g/m²/day up to 5days, max total dose 10 g/m² per course FLAG: Days 1-5: fludarabine 30 mg/m² IV for 30min, Days 1-5: cytarabine 1-2 grm/m² for 4hr daily x 5 & G-CSF 5 mcg/kg or 300 mcg/m² until PMN recovery, with or without idarubicin Days 1-3 at 8 mg/m² IV daily x 3 (FLAG-Ida) MEC: Days 1-6: mitoxantrone 6 mg/m² IV bolus, etoposide 80 mg/m² IV 1hr & cytarabine 1 grm/m² IV 6hr Intermediate DAC: cytarabine 20 mg/m² IV daily x 5
  • Cytarabine
  • Azacitidine
  • Decitabine
  • Mitoxantrone
  • Etoposide
  • Fludarabine
  • Idarubicin

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or pathologically confirmed diagnosis of AML based on World Health
             Organization (WHO) classification that has relapsed after, or is refractory to, two or
             three prior induction regimens that may have included intensive chemotherapy (e.g.,
             "7+3" cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or
             decitabine) , or targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal antibody).

             (Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts
             in peripheral blood 90 days to 24 months after first CR or CR without complete
             platelet recovery (CRp). Refractory AML is defined as persistent disease ≥28 days
             after initiation of intensive induction therapy (up to two induction cycles) or
             relapse <90 days after first CR or CRp. Refractory disease for patients undergoing
             hypomethylating agent induction is defined as lack of remission following at least 2
             cycles of epigenetic therapy without reduction in bone marrow blast status.)

          2. Aged ≥ 18 years.

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.

          4. Adequate clinical laboratory values (i.e., plasma creatinine < 2.5 x upper limit of
             normal (ULN) for the institution, bilirubin < 2.5 x ULN, alanine transaminase (ALT)
             and aspartate transaminase (AST) ≤ 2.5 x ULN).

          5. Absence of active central nervous system (CNS) involvement by leukemia. Patients with
             previously diagnosed CNS leukemia are eligible if the CNS leukemia is under control
             and intrathecal treatment may continue throughout the study.

          6. Absence of uncontrolled intercurrent illnesses, including uncontrolled infections,
             cardiac conditions, or other organ dysfunctions.

          7. Signed informed consent prior to the start of any study specific procedures.

          8. Women of child-bearing potential must have a negative serum or urine pregnancy test.

          9. Male and female patients must agree to use acceptable contraceptive methods for the
             duration of the study and for at least one month after the last drug administration.

        Exclusion Criteria:

          1. The interval from prior treatment to time of study drug administration is < 2 weeks
             for cytotoxic agents or < 5 half-lives for noncytotoxic agents. Exceptions: Use of
             hydroxyurea is allowed before the start of study and is to be discontinued prior to
             randomization. Hydroxyurea may be administered before study start and up to the time
             of study randomization. At the investigator's discretion, for patients with
             significant leukocytosis during the early treatment cycles, hydroxyurea may be
             administered. The hydroxyurea should be discontinued as soon as clinically
             appropriate.

          2. Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.

          3. Cardiac (left ventricular ejection fraction ≤40%) function.

          4. White blood cell (WBC) >15,000/uL.

          5. For patients with prior hematopoietic stem cell transplant (HSCT):

               1. Less than 3 months since HSCT

               2. Acute Graft versus Host Disease (GvHD) >Grade 1

               3. Chronic GvHD >Grade 1

          6. Any concomitant condition that in the opinion of the investigator could compromise the
             objectives of this study and the patient's compliance.

          7. A pregnant or lactating woman.

          8. Current malignancies of another type. Exceptions: Patients may participate if they
             have previously treated and currently controlled prostate cancer, or adequately
             treated in situ cervical cancer or basal cell skin cancer, or other malignancies with
             no evidence of disease for 2 years or more.

          9. Patient has acute promyelocytic leukemia (APL).

         10. Patients with known HIV, HBV or HCV infection (note: testing for these infections is
             not required).

         11. Documented or known clinically significant bleeding disorder.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission (CR) rate
Time Frame:3 years
Safety Issue:
Description:The rate of CR based on International Working Group (IWG) Guidelines for bone marrow and blood response

Secondary Outcome Measures

Measure:CR rate with partial hematologic recovery (CRh)
Time Frame:3 years
Safety Issue:
Description:CR as above including neutrophil granulocyte count > 0.5x10^9/L & platelet count > 50x10^9/L
Measure:CR rate with partial hematologic recovery (CRh) and incomplete platelet recovery (CRp)
Time Frame:3 years
Safety Issue:
Description:CR as above including neutrophil granulocyte count > 0.5x10^9/L & platelet count > 50x10^9/L + platelet count < 100x10^9/L
Measure:Duration of response
Time Frame:3 years
Safety Issue:
Description:Number of days from the time of initial response (CR, CRp, CRi, CRh or PR) to disease progression or death
Measure:Overall survival
Time Frame:3 years
Safety Issue:
Description:Number of days from date of first dose to date of death
Measure:Transition rate to stem cell transplantation (SCT)
Time Frame:3 years
Safety Issue:
Description:Number of subjects who transition to SCT
Measure:Overall response rate (ORR)
Time Frame:3 years
Safety Issue:
Description:The rate of CR + CRi + CRp + PR
Measure:Rate of disease related co-morbidities
Time Frame:3 years
Safety Issue:
Description:Number and severity of expected leukemia-related adverse events
Measure:Adverse events
Time Frame:3 years
Safety Issue:
Description:Number of patients with adverse events

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Delta-Fly Pharma, Inc.

Last Updated

December 16, 2019