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Study of Iomab-B Prior to HCT vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory AML (SIERRA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Actinium Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Actinium Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02665065
First received: January 22, 2016
Last updated: April 24, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Acute Myeloid Leukemia
Leukemia, Acute Myeloid
Myeloid Leukemia, Acute
Leukemia, Myeloid, Acute
Acute Myelogenous Leukemia
Leukemia, Acute Myelogenous
Myelogenous Leukemia, Acute
Drug: Iomab-B
Drug: Conventional Care
Drug: Fludarabine
Radiation: Total Body Irradiation
Procedure: HCT
Drug: Mycofenolate mofetil (MMF)
Drug: Cyclosporine or Tacrolimus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by Actinium Pharmaceuticals:

Primary Outcome Measures:
  • 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 [ Time Frame: 6 months from time of initial CR or CRp ]

Secondary Outcome Measures:
  • Overall Survival (OS) at 1 year from randomization [ Time Frame: 1-year following randomization ]

Estimated Enrollment: 150
Study Start Date: June 2016
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Iomab-B Drug: Fludarabine
30 mg/m2/day on days -4, -3, and -2 prior to transplant
Radiation: Total Body Irradiation
2 Gy on day of transplant
Procedure: HCT Drug: Mycofenolate mofetil (MMF)
On day 0 through day 28 (15mg/kg every 12 hours) for related donor and day 40 (15mg/kg every 8 hours) for unrelated donor (taper to day 96 in absence of GVHD)
Drug: Cyclosporine or Tacrolimus
Immunosuppression with either CSP or TAC starting 3 days prior to transplant and continuing with taper through 180 days post-transplant
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), 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, Etoposide, Fludarabine, Hydroxyurea (not allowed as a single agent), Idarubicin, L-Asparaginase, Mitoxantrone, Thioguanine
Drug: Conventional Care

  Eligibility

Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have active, relapsed or refractory Acute Myeloid Leukemia (AML). Active, relapsed or refractory AML is defined as either (1) primary induction failure (PIF) after 2 or more cycles of chemotherapy, (2 first early relapse after a remission duration of fewer than 6 months, (3) relapse refractory to salvage combination chemotherapy containing high-dose AraC, and (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 (Cockroft-Gault equation) > 50 mL/min
  • Have adequate hepatic function (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, HSC donor matching at human leukocyte antigen (HLA)-A, HLA-B, HLA-C, and DRB-1
  • For 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; For 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 clinical significant cardiomyopathy
  • Have abnormal QTcF (>450milliseconds) after electrolytes have been corrected (at least two different ECG readings and at least 15 minutes between readings)
  • Have known 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
  • 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. Exceptions to this exclusion include: treated non-melanoma skin cancer, 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 received an antibody therapy within 3 weeks
  • Have a perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
  • Currently receiving any other active investigational agents, with the exception of FLT3 inhibitors, such as sorafenib. FLT3 inhibitors can be administered until 3 days prior to the Therapeutic Infusion in the Iomab-B Treatment group and 3 days prior to the start of the salvage chemotherapy regimen in the Conventional Care Treatment group.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02665065

Contacts
Contact: Kevin Zikaras iomab@actiniumpharma.com

Locations
United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States
United States, Illinois
Loyola University Medical Center Recruiting
Maywood, Illinois, United States
United States, Kansas
The University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States
United States, Pennsylvania
Penn State Hershey Cancer Institute Recruiting
Hershey, Pennsylvania, United States
United States, Texas
Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States
MD Anderson Cancer Center Recruiting
Houston, Texas, United States
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States
Sponsors and Collaborators
Actinium Pharmaceuticals
Investigators
Study Director: Mark Berger, MD Actinium Pharmaceuticals
  More Information

Responsible Party: Actinium Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02665065     History of Changes
Other Study ID Numbers: Iomab-01
Study First Received: January 22, 2016
Last Updated: April 24, 2017

Keywords provided by Actinium Pharmaceuticals:
Acute Myeloid Leukemia
Leukemia, Acute Myeloid
Myeloid Leukemia, Acute
Bone Marrow Cell Transplantation
Transplantation, Bone Marrow
HCT
HSCT
Refractory AML
Relapsed AML
BC8
I-131
Iomab
Iomab-B
CD45
Iodine
Iodine-131
131-I
AML
BMT
radioimmunotherapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Tacrolimus
Cyclosporins
Cyclosporine
Fludarabine phosphate
Mycophenolate mofetil
Mycophenolic Acid
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on April 28, 2017