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Vadastuximab Talirine (SGN-CD33A; 33A) Combined With Azacitidine or Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (CASCADE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02785900
Recruitment Status : Terminated (Due to safety; specifically a higher rate of deaths, including fatal infections, in the SGN33A arm versus the control arm)
First Posted : May 30, 2016
Results First Posted : December 12, 2018
Last Update Posted : December 12, 2018
Sponsor:
Information provided by (Responsible Party):
Seattle Genetics, Inc.

Brief Summary:
The purpose of this study in AML patients is to test whether vadastuximab talirine (SGN-CD33A; 33A) combined with either azacitidine or decitabine improves remission rates and extends overall survival as compared to placebo combined with either azacitidine or decitabine.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: 33A Drug: placebo Drug: azacitidine Drug: decitabine Phase 3

Detailed Description:

Hypomethylating agents (HMAs), such as decitabine or azacitidine, are considered a standard treatment for older patients with AML. The primary goals of this study are to test whether patients treated with an HMA (either decitabine or azacitidine) in combination with 33A will have better anti-tumor activity and/or survive longer than patients treated with an HMA in combination with placebo.

Patients who meet eligibility criteria will be randomly assigned to one of two treatment groups: 1) 33A plus HMA (Experimental Arm); or 2) placebo plus HMA (Comparator Arm). In addition to evaluating survival and remission rates, the minimal residual disease (MRD)-negative remission rate, duration of remission, event free- and leukemia-free survival, and safety and tolerability will be compared between arms.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Phase 3 Study of Vadastuximab Talirine (SGN-CD33A) Versus Placebo in Combination With Azacitidine or Decitabine in the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Study Start Date : May 2016
Actual Primary Completion Date : October 3, 2017
Actual Study Completion Date : October 3, 2017


Arm Intervention/treatment
Experimental: 33A + HMA
33A plus azacitidine or decitabine
Drug: 33A
33A, 10 mcg/kg, every 4 weeks via intravenous (IV) push
Other Name: vadastuximab talirine, SGN-CD33A

Drug: azacitidine
75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks

Drug: decitabine
20 mg/m2 given IV x 5 days, every 4 weeks

Active Comparator: placebo + HMA
placebo plus azacitidine or decitabine
Drug: placebo
Volume equivalent to 10 mcg/kg, every 4 weeks via IV push

Drug: azacitidine
75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks

Drug: decitabine
20 mg/m2 given IV x 5 days, every 4 weeks




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 1.5 years ]
    Time from randomization to death due to any cause

  2. Composite Complete Remission (CRc) Rate [ Time Frame: Up to 1.5 years ]
    Number of patients who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) according to the modified response criteria for acute myeloid leukemia (AML) per Cheson 2003.


Secondary Outcome Measures :
  1. Minimal Residual Disease (MRD)-Negative Composite Complete Remission Rate [ Time Frame: Up to 1.5 years ]
    Number of patients who achieve both remission (CR or CRi) and MRD-negative status

  2. Duration of Remission [ Time Frame: Up to approximately 9.5 months ]
    Duration of remission is calculated from the first documentation of CR or CRi to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.

  3. Event-free Survival [ Time Frame: Up to approximately 11.24 months ]
    Event-free survival is calculated from the time of randomization to the first documentation of progression, relapse, or death, whichever comes first. Patients who do not have event (progression, relapse, or death) prior to analysis cutoff date are censored at the date of last response assessment. Patients who started another anticancer therapy before progression, relapse, or death are censored at the date of last response assessment prior to the start of new therapy. Patients who do not have response assessment post-baseline are censored at the date of randomization.

  4. Leukemia-free Survival [ Time Frame: Up to approximately 9.49 months ]
    Leukemia-free survival is calculated from the first documentation of blast clearance (CR, CRi, mLFS) to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.

  5. Type, Incidence, Severity, Seriousness, and Relatedness of Adverse Events [ Time Frame: Up to 1.5 years ]
    Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. SAE = serious adverse event. "Study treatment" in this data set refers to blinded study treatment.

  6. Incidence of Grade 3 or Higher Laboratory Abnormalities [ Time Frame: Up to 1.5 years ]
    Participants who experienced a laboratory grade increase to Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE], v4.03)

  7. Time to Complete Remission [ Time Frame: Up to 1.5 years ]
    Time to CR or CRi is the time from randomization to the first documentation of CR/CRi

  8. Mortality Rates at Day 30 and Day 60 [ Time Frame: Up to 60 days ]
    30- and 60-day survival from date of randomization. Estimated using Kaplan-Meier method.



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:

  • Newly diagnosed, previously untreated, cytologically/histologically confirmed de novo or secondary AML according to World Health Organization (WHO) classification (except for acute promyelocytic leukemia (APL))
  • Intermediate or adverse cytogenetic risk
  • Eligible for therapy with either decitabine or azacitidine
  • Acceptable hematologic and organ function

Exclusion Criteria:

  • AML associated with favorable risk karyotypes including inv(16), t(8;21), t(16;16), or t(15;17)
  • Patients who are candidates for allogeneic stem cell transplant at the time of enrollment
  • Patients with a history of one of the following myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, and primary myelofibrosis
  • Received prior treatment with HMA or chemotherapy for antecedent myelodysplastic syndrome (MDS)

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): NCT02785900


Locations
Show Show 128 study locations
Sponsors and Collaborators
Seattle Genetics, Inc.
Investigators
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Study Director: Phoenix Ho, MD Seattle Genetics, Inc.
  Study Documents (Full-Text)

Documents provided by Seattle Genetics, Inc.:
Statistical Analysis Plan  [PDF] December 4, 2017
Study Protocol  [PDF] March 27, 2017

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Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT02785900    
Other Study ID Numbers: SGN33A-005
2015-003482-28 ( EudraCT Number )
First Posted: May 30, 2016    Key Record Dates
Results First Posted: December 12, 2018
Last Update Posted: December 12, 2018
Last Verified: November 2018
Keywords provided by Seattle Genetics, Inc.:
Antibodies, monoclonal
Antibody drug conjugate
Antigens, cluster of differentiation 33 (CD33)
Drug therapy
Immunotherapy
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors