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Low Dose Cytarabine and Lintuzumab-Ac225 in Older AML Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Actinium Pharmaceuticals
Information provided by (Responsible Party):
Actinium Pharmaceuticals Identifier:
First received: October 7, 2015
Last updated: October 25, 2015
Last verified: October 2015

The study is a multicenter, open label Phase I/II trial.

The goal of the Phase I part of this study is to find the highest tolerable dose of Lintuzumab-Ac225 that can be given with cytarabine to patients with AML.

The goal of the Phase II part of this study is to learn if Lintuzumab-Ac225 and cytarabine can control AML. The safety of this drug combination will also be studied.

Lintuzumab-Ac225 is designed to deliver radiation therapy directly inside leukemia cells without giving any radiation to the surrounding normal cells

Cytarabine is designed to insert itself into DNA (genetic material) of cancer cells and stop the DNA from repairing itself.

Condition Intervention Phase
Drug: Cytarabine
Biological: Lintuzumab-Ac225
Drug: Furosemide
Drug: Spironolactone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia

Resource links provided by NLM:

Further study details as provided by Actinium Pharmaceuticals:

Primary Outcome Measures:
  • Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 [ Time Frame: Cycle 1, up to 52 days ] [ Designated as safety issue: Yes ]
    If two or more patients in a cohort experience dose limiting toxicity (DLT), then maximum tolerated dose (MTD) will have been exceeded, and no further dose escalation will occur. If only three patients were treated at a dose level under consideration as the MTD, then up to three additional patients will be accrued. If no more than one of the six patients at that dose level experiences DLT, then that dose level will be confirmed as the MTD.

  • Phase II: CR+CRp [ Time Frame: Up to 22 weeks from enrollment ] [ Designated as safety issue: No ]
    The primary objective is to determine the antileukemic effects, including its ability to produce complete remissions, of Lintuzumab-Ac225.

Secondary Outcome Measures:
  • Phase II: PFS [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Progression Free Survival

  • Phase II: LFS [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Leukemia Free Survival

  • Phase II: OS [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Overall Survival

  • Phase II: Toxicity Spectrum [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 72
Study Start Date: October 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Drug

Experimental: Cytarabine + Lintuzumab-Ac225 Cytarabine 20 mg subq every 12h, days 1 to 10 of each cycle. Starting dose 1.0 μCi/Kg Lintuzumab-Ac225 and 15 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given approx. 4-7 days after 1 cycle of low dose cytarabine and the second fraction given 4-7 days after the first fraction, followed by up to 11 more cycles. Lasix 40 mg po daily one day prior to treatment with Lintuzumab-Ac225 and continuing for 10 days following administration of the 2nd divided dose. Spironolactone, 25 mg po daily, given 11 days after second dose of 225Ac-HuM195 (the day after furosemide completion) and continued for 12 months.


  • Drug: Cytarabine
  • Biological: Lintuzumab-Ac225
  • Drug: Furosemide
  • Drug: Spironolactone
Drug: Cytarabine
Low dose cytarabine administered at 20 mg subcutaneously every 12 hours for the first 10 days (Days 1 to 10) of every cycle. Cycle 1 can last up to 52 days (depending on the schedule of study drug dosing) in order to allow for recovery from Lintuzumab-Ac225. Cycles 2-12 will last 28 days each.
Other Names:
  • Cytosar
  • Ara-C
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Low dose Ara-C
  • LDAC
Biological: Lintuzumab-Ac225
Starting dose level 1.0 μCi/Kg of Lintuzumab-Ac225 and 15 μg/Kg unlabeled HuM195 divided into 2 equal fractionated doses (0.5 μCi/Kg and 7.5 μg /Kg + 0.5 μCi/Kg and 7.5 μg /Kg) with the first fraction administered approximately 4-7 days after 1 cycle of low dose cytarabine and the second fraction administered 4-7 days after the first fraction, followed by up to 11 more cycles.
Other Names:
  • Lintuzumab
  • HuM195
  • HuM195-Ac225
  • Actimab-A
  • Actimab
  • 225Ac-HuM195
Drug: Furosemide
40 mg by mouth daily one day prior to treatment with Lintuzumab-Ac225 and continuing for 10 days following administration of the 2nd divided dose.
Other Name: Lasix
Drug: Spironolactone
25 mg by mouth daily, administered 11 days after second dose of 225Ac-HuM195 (the day after completion of furosemide) and continued for 12 months.
Other Name: Aldactone

  Show Detailed Description


Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Untreated AML, including patients with an antecedent hematologic disorder or secondary disease. Patients with prior MDS may have received therapy with immunomodulatory agents or hypomethylating agents for this diagnosis. Patients with other prior cancer diagnoses are allowed as long as they have no measurable disease are not undergoing active therapy, and have a life expectancy of ≥ 4 months.
  2. Patients age ≥60 years who:

    1. Are unwilling to receive intensive (e.g. 7+3) chemotherapy, or
    2. Have poor-risk prognostic factors defined as antecedent hematologic disorder, prior chemotherapy or XRT, abnormal karyotype other than t(8;21), inv16, or t(16;16), any karyotype with FLT3-ITD, or presenting WBC>100K, or
    3. Have significant comorbidities, that in the judgment of the investigator makes the subject unsuitable for standard dose induction chemotherapy (e.g. anthracycline and infusional cytarabine given as 7+3), or;
    4. Any patient age ≥ 70 years.
  3. Blast count ≥20%
  4. Greater than 25% of blasts must be CD33 positive.
  5. Adequate renal and hepatic function
  6. ECOG ≤ 3

Exclusion Criteria:

  1. Patients with acute promyelocytic leukemia
  2. Treatment with chemotherapy or biologic therapy within 3 weeks, except for hydroxyurea, which must be discontinued prior to treatment on study
  3. Treatment with radiation within 6 weeks
  4. Active serious infections uncontrolled by antibiotics
  5. Active malignancy within 2 years of entry, except previously treated non-melanoma skin cancer, carcinoma in situ or cervical intraepithelial neoplasia, and organ confined prostate cancer with no evidence of progressive disease based on PSA levels and are not on active therapy.
  6. Clinically significant cardiac or pulmonary disease
  7. Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
  8. Psychiatric disorder that would preclude study participation
  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 identifier: NCT02575963

Contact: Dragan Cicic, MD 646-459-4201

United States, Maryland
Johns Hopkins Medicine Recruiting
Baltimore, Maryland, United States, 21231
Contact: B. Douglas Smith, MD    410-955-8964   
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Jae Park, MD    646-497-9154   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Alexander Perl, MD    215-573-8478   
United States, Texas
Baylor Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: M. Yair Levy, MD    214-370-1000   
United States, Washington
Fred Hutchinson Cancer Research Center / Seattle Cancer Care Alliance Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Johnnie Orozco, MD PhD    206-667-4886   
Sponsors and Collaborators
Actinium Pharmaceuticals
Principal Investigator: Jae Park, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: M. Yair Levy, MD Baylor College of Medicine
Study Chair: Joseph Jurcic, MD Columbia University
Principal Investigator: B. Douglas Smith, MD Kimmel Cancer Center at Johns Hopkins
Principal Investigator: Johnnie Orozco, MD PhD Fred Hutchinson Cancer Research Center
Principal Investigator: Alexander Perl University of Pennsylvania
  More Information

Responsible Party: Actinium Pharmaceuticals Identifier: NCT02575963     History of Changes
Obsolete Identifiers: NCT01756677
Other Study ID Numbers: API-01 
Study First Received: October 7, 2015
Last Updated: October 25, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing
Natriuretic Agents
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators processed this record on October 21, 2016