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Acute Myeloid LeukemiaPhase 3SIERRANCT02665065

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

A Phase 3 study testing Iomab-B, Conventional Care and HCT in people with Acute Myeloid Leukemia and Leukemia, Acute Myeloid, run by Actinium Pharmaceuticals at 24 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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… Read more about this study

Who is it for?
Ages 55 years and older
What is being tested?
Iomab-B, Conventional Care and HCT
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
24 sitesin 2 countries
Study dates
Jun 2016to Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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])
Show all 12Show fewer
  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States22 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of North Carolina Hospital

    Chapel Hill, North Carolina, 27599

  • University Hospital of Cleveland Seidman Cancer Center

    Cleveland, Ohio, 44106

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Yale Cancer Center

    New Haven, Connecticut, 06520

  • Weill Cornell Medicine

    New York, New York, 10022

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10038

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68106

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55902

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stony Brook University

    Stony Brook, New York, 11794

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • The University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

Canada2 sites

  • University of Ottawa

    Ottawa, Ontario

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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)

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).

Read the 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.

Being tested
Iomab-B, Conventional Care, HCT
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
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iomab-BDrug

  • Conventional CareDrug

  • HCTProcedure or surgery

Study groups in NCT02665065
Study groupRoleWhat they receive
Iomab-BExperimentalIomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT
Receives: Drug: Iomab-B; Procedure: HCT
Conventional CareActive comparatorDefined 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.
Receives: Drug: Conventional Care; Procedure: HCT

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 months from time of initial CR or CRp

Secondary outcomes (2)

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

    Patient overall survival

    Measured: Over a 5 year period

  2. Event-Free Survival

    Duration of time from randomization to the date of induction treatment failure (ITF), relapse or death

    Measured: Over a 5 year period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionJun 2022
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02665065
Sponsor's protocol ID
Iomab-01
Acronym
SIERRA
Status last verified
Jul 2023
First submitted
22 Jan 2016
Last updated
19 Jul 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 39298738

  • 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.

    PubMed 35350938

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Iomab-B, Conventional Care and HCT in people with Acute Myeloid Leukemia and Leukemia, Acute Myeloid, run by Actinium Pharmaceuticals at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Durable Complete Remission (dCR) (time frame: 6 months from time of initial CR or CRp). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02665065, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.

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