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

NCT02665065 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: Iomab-01
• Study Type: interventional
• Target: 153
• Locations: 2 countries
• Sites: 24

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).

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall Survival (OS) following randomization to Iomab-B versus Convetional Care

  Over a 5 year period

• Event-Free Survival

  Over a 5 year period

Study Arms (2)

Iomab-B

EXPERIMENTAL

Iomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT

Drug: Iomab-B; Procedure: HCT

Conventional Care

ACTIVE COMPARATOR

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.

Drug: Conventional Care; Procedure: HCT

Interventions

Iomab-B DRUG

Iomab-B

Conventional Care DRUG

Conventional Care

HCT PROCEDURE

Conventional Care; Iomab-B

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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 a perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
• Currently receiving any other active investigational agents

Sponsors & Collaborators

• Actinium Pharmaceuticals: lead

Study Sites (24)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medicine

New York, New York, 10022, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10038, United States

Location

Stony Brook University

Stony Brook, New York, 11794, United States

Location

University of North Carolina Hospital

Chapel Hill, North Carolina, 27599, United States

Location

University Hospital of Cleveland Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University of Ottawa

Ottawa, Ontario, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (2)

• Gyurkocza B, Nath R, Seropian S, Choe H, Litzow MR, Abboud C, Koshy N, Stiff P, Tomlinson B, Abhyankar S, Foran J, Hari P, Chen G, Al-Kadhimi Z, Kebriaei P, Sabloff M, Orozco JJ, Jamieson K, Silverman M, Van Besien K, Schuster M, Law AD, Larkin K, Pandit-Taskar N, Rowley SD, Munshi P, Cook R, Levy MY, Lazarus HM, Sandmaier BM, Pagel JM, Reddy V, MacDougall J, McNamara K, Spross J, Haeuber E, Vusirikala M, Nahar A, Desai A, Giralt S. Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML. J Clin Oncol. 2025 Jan 10;43(2):201-213. doi: 10.1200/JCO.23.02018. Epub 2024 Sep 19.

  PMID: 39298738 DERIVED

• 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.

  PMID: 35350938 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Avinash Desai, MD

  Actinium Pharmaceuticals

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2016
• First Posted: January 27, 2016
• Study Start: June 1, 2016
• Primary Completion: June 1, 2022
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 19, 2023

Record last verified: 2023-07

Locations

US (22); CA (2)