Clinical Trials /

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

NCT02665065

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Iomab-B Prior to HCT vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory AML
  • 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

Clinical Trial IDs

  • ORG STUDY ID: Iomab-01
  • NCT ID: NCT02665065

Conditions

  • Acute Myeloid Leukemia
  • Leukemia, Acute Myeloid
  • Myeloid Leukemia, Acute
  • Leukemia, Myeloid, Acute
  • Acute Myelogenous Leukemia
  • Leukemia, Acute Myelogenous
  • Myelogenous Leukemia, Acute

Interventions

DrugSynonymsArms
Iomab-BIomab-B
Conventional CareConventional Care

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.

Trial Arms

NameTypeDescriptionInterventions
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
  • Iomab-B
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, 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.
  • Conventional Care

Eligibility 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, medically cleared HSC donor matching at
             human leukocyte antigen (HLA)-A, HLA-B, HLA-C, and DRB-1

          -  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

          -  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 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

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:55 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival (OS) at 1 year from randomization
Time Frame:1-year following randomization
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Actinium Pharmaceuticals

Trial Keywords

  • 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

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