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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/27/2021.

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

Clinicaltrials.gov identifier NCT03926624

Recruitment Status Recruiting

First Posted April 24, 2019

Last update posted July 2, 2020

Study Description

Brief summary:

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.

  • Condition or Disease:Leukemia, Myeloid, Acute
  • Intervention/Treatment: Drug: DFP-10917
    Drug: Cytarabine
    Drug: Azacitidine
    Drug: Decitabine
    Drug: Mitoxantrone
    Drug: Etoposide
    Drug: Fludarabine
    Drug: Idarubicin
  • Phase: Phase 3
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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 450 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Intervention Model Description: randomized, controlled
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • 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
  • Actual Study Start Date: November 2019
  • Estimated Primary Completion Date: December 2022
  • Estimated Study Completion Date: December 2022
Arms and interventions
Arm Intervention/treatment
Experimental: Experimental
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
Drug: DFP-10917
DFP-10917 Powder for Injection. Active ingredient: 4-amino-1-(2-cyano-deoxy-β-D-arabinofuranosyl)-2(1H)-pyrimidinone monohydrochloride
Active Comparator: Control
Non-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
Drug: Cytarabine
cytosine arabinoside (ara-C)

Drug: Azacitidine
Azacitidine

Drug: Decitabine
Decitabine

Drug: Mitoxantrone
Mitoxantrone

Drug: Etoposide
Etoposide

Drug: Fludarabine
Fludarabine

Drug: Idarubicin
Idarubicin
Outcome Measures
  • Primary Outcome Measures: 1. Complete remission (CR) rate [ Time Frame: 3 years ]
    The rate of CR based on International Working Group (IWG) Guidelines for bone marrow and blood response
  • 2. Duration of complete remission [ Time Frame: 3 years ]
    Number of days from time of initial CR until disease recurrence or death
  • Secondary Outcome Measures: 1. CR rate with partial hematologic recovery (CRh) [ Time Frame: 3 years ]
    CR as above including neutrophil granulocyte count > 0.5x10^9/L & platelet count > 50x10^9/L
  • 2. CR rate with partial hematologic recovery (CRh) and incomplete platelet recovery (CRp) [ Time Frame: 3 years ]
    CR as above including neutrophil granulocyte count > 0.5x10^9/L & platelet count > 50x10^9/L + platelet count < 100x10^9/L
  • 3. Duration of response [ Time Frame: 3 years ]
    Number of days from the time of initial response (CR, CRp, CRi, CRh or PR) to disease progression or death
  • 4. Overall survival [ Time Frame: 3 years ]
    Number of days from date of first dose to date of death
  • 5. Transition rate to stem cell transplantation (SCT) [ Time Frame: 3 years ]
    Number of subjects who transition to SCT
  • 6. Overall response rate (ORR) [ Time Frame: 3 years ]
    The rate of CR + CRi + CRp + PR
  • 7. Rate of disease related co-morbidities [ Time Frame: 3 years ]
    Number and severity of expected leukemia-related adverse events
  • 8. Adverse events [ Time Frame: 3 years ]
    Number of patients with adverse events
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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 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.

Contacts and Locations
Contacts

Contact: Kiran Naqvi 7137455073 knaqvi@mdanderson.org

Locations
Show 17 Study Locations
Sponsors and Collaborators

Delta-Fly Pharma, Inc.

Investigators

Principal Investigator: Kiran Naqvi, MD M.D. Anderson Cancer Center

More Information
  • Responsible Party: Delta-Fly Pharma, Inc.
  • ClinicalTrials.gov Identifier: NCT03926624 History of Changes
  • Other Study ID Numbers: D18-11141
  • First Posted: April 24, 2019 Key Record Dates
  • Last Update Posted: July 2, 2020
  • Last Verified: July 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute