Clinical trial NCT02665065: Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: 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
Keywords: Acute Myeloid Leukemia
Leukemia, Acute Myeloid
Myeloid Leukemia, Acute
Bone Marrow Cell Transplant
Transplant, Bone Marrow
HCT
HSCT
Refractory AML
Relapsed AML
BC8
I-131
Iomab
Iomab-B
CD45
Iodine
Iodine-131
131-I
AML
BMT
Radioimmunotherapy
Lead sponsor: Actinium Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-01-27
Enrollment: 153
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 following randomization to Iomab-B, as well as Event-Free Survival. 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.

Eligibility criteria: 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, 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 with a donor who is medically cleared. Syngeneic donors that meet these criteria are allowed
* 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 (including both allogeneic and autologous 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

Primary outcomes:
measure: Durable Complete Remission (dCR)
timeFrame: 6 months from time of initial CR or CRp
Secondary outcomes:
measure: Overall Survival (OS) following randomization to Iomab-B versus Convetional Care
timeFrame: Over a 5 year period
measure: Event-Free Survival
timeFrame: Over a 5 year period
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital
state: North Carolina
city: Cleveland
country: United States
facility: University Hospital of Cleveland Seidman Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Actinium Pharmaceuticals
name: Avinash Desai, MD
role: STUDY_CHAIR
References:
citation: Walter RB. Where do we stand with radioimmunotherapy for acute myeloid leukemia? Expert Opin Biol Ther. 2022 May;22(5):555-561. doi: 10.1080/14712598.2022.2060735. Epub 2022 Mar 31.