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

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ClinicalTrials.gov Identifier: NCT03926624
Recruitment Status : Recruiting
First Posted : April 24, 2019
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
Delta-Fly Pharma, Inc.

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 Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: DFP-10917 Drug: Cytarabine Drug: Azacitidine Drug: Decitabine Drug: Mitoxantrone Drug: Etoposide Drug: Fludarabine Drug: Idarubicin 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.


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Study Type : Interventional  (Clinical Trial)
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
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022


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




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 < 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03926624


Contacts
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Contact: Kiran Naqvi 7137455073 knaqvi@mdanderson.org

Locations
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United States, Arizona
Banner MD Anderson Recruiting
Gilbert, Arizona, United States, 85234
Contact: Andrea Winkle, RN, BSN    480-256-3421      
Principal Investigator: Rajneesh Nath, MD         
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Bruck Habtemarjam    310-794-0242    bhabtemariam@mednet.ucla.edu   
Principal Investigator: Gary Schiller, MD         
United States, District of Columbia
George Washington University Not yet recruiting
Washington, District of Columbia, United States, 20052
Contact: Monica Rengifo-Pardo    202-994-1161    mrengifopardo@mfa.gwu.edu   
Principal Investigator: Imad Tabbara, MD         
United States, Florida
Baptist MD Anderson Recruiting
Jacksonville, Florida, United States, 32207
Contact: Carol Fairchild    419-320-3298    Carol.Fairchild@bmcjax.com   
Principal Investigator: William Hammond, MD         
United States, Illinois
Rush University Not yet recruiting
Chicago, Illinois, United States, 60612
Contact: Angela Yecke    312-942-5798    Angela_Yecke@rush.edu   
Principal Investigator: Melissa Larson, MD         
Loyola University Medical Center Not yet recruiting
Hines, Illinois, United States, 60153
Contact: Stephanie Martin, RN, BSN    708-327-3095    smartin19@luc.edu   
Principal Investigator: Stephanie Tsai, MD         
United States, Kentucky
Norton Cancer Institute Not yet recruiting
Louisville, Kentucky, United States, 40241
Contact: Joseph Maly    502-899-3366    joseph.maly@nortonhealthcare.org   
United States, Louisiana
Ochsner Benson Cancer Center Not yet recruiting
Jefferson, Louisiana, United States, 70121
Contact: Melissa Forschler    504-842-3918    melissa.forschler@ochsner.org   
Contact: Elise Curry    504-842-8084    elisemarie.curry@ochsner.org   
Principal Investigator: Laura Finn, MD         
Tulane University Not yet recruiting
New Orleans, Louisiana, United States, 70118
Contact: Elise Tatje    504-988-2987    etatje@tulane.edu   
Principal Investigator: Hana Safah, MD         
United States, Missouri
St. Luke's Cancer Institute Not yet recruiting
Kansas City, Missouri, United States, 64111
Contact: Andrea Watson    916-932-2677    Slciresearch1@saint-lukes.org   
Principal Investigator: Shahzad Raza, MD         
United States, New York
SUNY- Stony Brook Not yet recruiting
Stony Brook, New York, United States, 11794
Contact: Aisha Hashmi       cancerclinicaltrials@stonybrookmedicine.edu   
Principal Investigator: Michael Schuster, MD         
New York Medical College Not yet recruiting
Valhalla, New York, United States, 10595
Contact: Kyaw Swa    914-493-8375    kswa@nymc.edu   
Contact: Paul Baskind    914-493-8375    paul_baskind@nymc.edu   
Principal Investigator: Karen Seitar, MD         
United States, Texas
UT Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Julie Zuckerman    214-648-5567    Julie.zuckerman@utsouthwestern.edu   
Principal Investigator: Prapti Patel, MD         
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kiran Naqvi, MD    713-745-5073    knaqvi@mdanderson.org   
United States, Vermont
University of Vermont Medical Center Not yet recruiting
Burlington, Vermont, United States, 05401
Contact: Jane Walsh    802-656-9926    Jane.e.walsh@uvm.edu   
Principal Investigator: Diego Adrianzen-Herrera, MD         
United States, Virginia
University of Virginia Health System Not yet recruiting
Charlottesville, Virginia, United States, 22903
Contact: Cory Caldwell    434-297-4182    CJC2P@virginia.edu   
Sponsors and Collaborators
Delta-Fly Pharma, Inc.
Investigators
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Principal Investigator: Kiran Naqvi, MD M.D. Anderson Cancer Center

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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: November 15, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Fludarabine
Fludarabine phosphate
Etoposide
Etoposide phosphate
Azacitidine
Decitabine
Mitoxantrone
Idarubicin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Analgesics
Sensory System Agents
Peripheral Nervous System Agents