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

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Subjects with secondary AML or treatment-related AML are eligible provided all inclusion criteria are met.
  • For clarification of criteria above:
    • Active disease is considered as bone marrow blast count > 5% or the presence of peripheral blasts;
    • Subjects with secondary AML or treatment-related AML are eligible.
  • Primary induction failure is defined as failure to achieve remission after:
    • Two or more cycles of high-dose cytotoxic chemotherapy; or
    • For patients with a TP53 mutation:
      • one cycle of high-dose cytotoxic chemotherapy and a 10-day regimen of decitabine (in either order; Welch, 2016); or
      • two or more cycles of a 10-day regimen of decitabine (Welch, 2016); or
      • two or more cycles of venetoclax in combination with azacitidine or decitabine (Maiti, 2019).
  • Duration of remission is defined as first confirmed complete response by bone marrow aspirate to first presence of peripheral blasts or bone marrow blast count > 5%.
  • High-dose cytarabine for the older patient population enrolled in this trial would be generally considered as a dose of 1000mg/m^2 or above.
  • Have documented CD45 expression by leukemic cells via flow cytometry (a “blast gate” on CD45 vs. side scatter analysis consistent with AML).
  • Be ≥ 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 (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 day.
  • 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 HLA-A, HLA-B, HLA-C, and DRB1.
  • 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 CSF by morphology or flow cytometry and/or any chloromas detected by CNS imaging.
  • Have previously received a HCT.
  • 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 (> 450 milliseconds) 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 judgment with cardiology consultation and clearance.
  • 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 cytogenetic 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 of randomization.
  • Have a perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation.
  • Currently receiving any other active investigational agents.

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

James Foran, M.D.

Open for enrollment

Contact information:

James Foran M.D.

(904)953-6153

Foran.James@mayo.edu

Rochester, Minn.

Mayo Clinic principal investigator

Mark Litzow, M.D.

Open for enrollment

Contact information:

Osha Grant

(507)284-6344

Grant.Osha@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20359599

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