Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

— SIERRA  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02665065
• Other study ID #: Iomab-01
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 2016
• Est. completion date: December 2026

Study information

• Verified date: July 2023
• Source: Actinium Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 153
• Est. completion date: December 2026
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Disease
• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia
• AML
• Bone Marrow Transplant
• Leukemia
• Leukemia, Acute Myelogenous
• Leukemia, Acute Myeloid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelogenous Leukemia, Acute
• Myeloid Leukemia, Acute

Intervention

Drug:
• Iomab-B

• Conventional Care

Procedure:
• HCT

Locations

Country	Name	City	State
Canada	University of Ottawa	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina Hospital	Chapel Hill	North Carolina
United States	University Hospital of Cleveland Seidman Cancer Center	Cleveland	Ohio
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic	Jacksonville	Florida
United States	Loyola University Medical Center	Maywood	Illinois
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stony Brook University	Stony Brook	New York
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Actinium Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Durable Complete Remission (dCR)	Defined as CR or CRp lasting 180 days or more from time of initial CR or CRp is documented with evidence of subsequent relapse	6 months from time of initial CR or CRp
Secondary	Overall Survival (OS) following randomization to Iomab-B versus Convetional Care	Patient overall survival	Over a 5 year period
Secondary	Event-Free Survival	Duration of time from randomization to the date of induction treatment failure (ITF), relapse or death	Over a 5 year period