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Study of Iomab-B Prior to Hematopoietic Cell Transplant vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (SIERRA in AML)

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ClinicalTrials.gov Identifier: NCT02665065
Recruitment Status : Recruiting
First Posted : January 27, 2016
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Actinium Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE January 22, 2016
First Posted Date  ICMJE January 27, 2016
Last Update Posted Date February 5, 2020
Study Start Date  ICMJE June 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 27, 2019)
Durable Complete Remission (dCR) [ Time Frame: 6 months from time of initial CR or CRp ]
Defined as CR or CRp lasting 180 days or more from time of initial CR or CRp is documented with evidence of subsequent relapse
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2016)
Durable Complete Remission (dCR) [ Time Frame: 6 months from hematopoietic stem cell transplant (HCT) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2019)
Overall Survival (OS) at 1 year from randomization [ Time Frame: 1-year following randomization ]
Patient overall survival
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2016)
Overall Survival (OS) [ Time Frame: 1-year period following treatment with study drug ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Iomab-B Prior to Hematopoietic Cell Transplant vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia
Official Title  ICMJE A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplant Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (AML)
Brief Summary The primary objective of this study is to demonstrate the efficacy of Iomab-B, in conjunction with a Reduced Intensity Conditioning (RIC) regimen and protocol-specified allogeneic hematopoietic stem cell transplant (HCT), versus Conventional Care in patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (AML).
Detailed Description SIERRA is a pivotal Phase 3 randomized controlled study of Iomab-B in Relapsed or Refractory AML patients. The SIERRA trial has a primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Leukemia, Acute Myeloid
  • Myeloid Leukemia, Acute
  • Leukemia, Myeloid, Acute
  • Acute Myelogenous Leukemia
  • Leukemia, Acute Myelogenous
  • Myelogenous Leukemia, Acute
  • AML
  • Bone Marrow Transplant
Intervention  ICMJE
  • Drug: Iomab-B
  • Drug: Conventional Care
  • Procedure: HCT
Study Arms  ICMJE
  • Experimental: Iomab-B
    Iomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT
    Interventions:
    • Drug: Iomab-B
    • Procedure: HCT
  • Active Comparator: Conventional Care
    Defined as Investigator's choice of salvage chemotherapy with any combination of the following agents: Azacitidine (not allowed as a single agent), Carboplatin, Cladribine, Clofarabine, Cyclophosphamide, Cytarabine, Daunorubicin, Decitabine (not allowed as a single agent with the exception of patients with documented TP53 mutations who have not previously received 10-day regimens of single agent decitabine), Doxorubicin, Enasidenib, Etoposide, Fludarabine, Gemtuzumab ozogamicin, Idarubicin, Ivosidenib (for subjects with IDH1 mutation), L-Asparaginase, Midostaurin (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Mitoxantrone, Sorafenib (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Thioguanine, Topotecan, Venetoclax (in combination with a hypomethylating agent). Chemotherapy agents not listed above may be administered after providing clinical justification and receiving medical monitor approval prior to initiation of treatment.
    Interventions:
    • Drug: Conventional Care
    • Procedure: HCT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 26, 2016)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have active, relapsed or refractory Acute Myeloid Leukemia (AML). Active, relapsed or refractory AML is defined as any one of the following (1) primary induction failure, or (PIF) after 2 or more cycles of therapy, or (2) first early relapse after a remission duration of fewer than 6 months, or (3) relapse refractory to salvage combination chemotherapy containing high-dose AraC, or (4) second or subsequent relapse
  • Have documented CD45 expression by leukemic cells via flow cytometry (a "blast gate" on CD45 vs. side scatter analysis consistent with AML)
  • Be at least 55 years of age
  • Have a circulating blast count of less than 10,000/mm3 (control with hydroxyurea is allowed)
  • Have a calculated creatinine clearance (Cockcroft-Gault equation) > 50 mL/min
  • Have adequate hepatic function (direct bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), defined as ≤ 2 times the upper limit of normal [ULN])
  • Have a Karnofsky score ≥ 70
  • Have an expected survival of > 60 days
  • Have a central venous catheter line in place prior to study treatment administration
  • Have 8/8 allele-level, related or unrelated, medically cleared HSC donor matching at human leukocyte antigen (HLA)-A, HLA-B, HLA-C, and DRB-1
  • Women of childbearing potential, be surgically sterile or agree to practice abstinence or utilize acceptable contraception (intrauterine, injectable, transdermal, or combination oral contraceptive) through 1-year post transplant; Males who are sexually active with women of childbearing potential must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) from time of screening through 12 weeks after last dose of study drug
  • Be able to understand the study procedures, agree to participate in the study program, and voluntarily provide written Informed Consent

Exclusion Criteria:

  • Have circulating HAMA noted on initial screening
  • Have received prior radiation to maximally tolerated levels to any critical normal organ
  • Have active leukemic central nervous system (CNS) involvement, as defined by any leukemic blasts detected in the cerebrospinal fluid (CSF) by morphology or flow cytometry and/or any chloromas detected by CNS imaging
  • Have previously received HCT
  • Have clinically significant cardiac disease (NYHA Class III or IV); clinically significant arrhythmia i.e. ventricular tachycardia, ventricular fibrillation, or "Torsade de Pointes". Myocardial infarction with uncontrolled angina within 6 months, congestive heart failure, or clinically significant cardiomyopathy
  • Have abnormal QTcF (>450milliseconds) after electrolytes have been corrected (at least two different ECG readings and at least 15 minutes between readings). Subjects with paced rhythm or prolonged QTcF may be exempt from this exclusion if considered eligible for transplant per treating physician clinical judgement with optional cardiology consultation
  • Have current or prior positive test results for human immunodeficiency virus (HIV) or hepatitis B (HBV) or C. Subjects who have positive HBV test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti- hepatitis B core protein (HBc) and positive antibody to the HBsAg (anti-HBs) are not excluded. Subjects who have positive hepatitis test results with adequate organ function as defined in the protocol are not excluded
  • Have active serious infection uncontrolled by antibiotics or antifungals
  • Have acute promyelocytic leukemia and the associated cytogenic translocation t(15/17)
  • Have active malignancy within 2 years of entry. Active malignancy is defined as those malignancies requiring treatment with anti-cancer therapy or in the event of indolent malignancies, having measurable disease. Exceptions to this exclusion include: myelodysplastic syndrome, treated non-melanoma skin cancer, completely resected Stage 0 or 1 melanoma no less than 1 year from resection, carcinoma in situ or cervical intraepithelial neoplasia, and successfully treated organ-confined prostate cancer with no evidence of progressive disease based on prostate specific antigen (PSA) levels and are not on active therapy
  • Have a perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
  • Currently receiving any other active investigational agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vijay Reddy, MD vreddy@actiniumpharma.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02665065
Other Study ID Numbers  ICMJE Iomab-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Actinium Pharmaceuticals
Study Sponsor  ICMJE Actinium Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mark Berger, MD Actinium Pharmaceuticals
PRS Account Actinium Pharmaceuticals
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP