This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Actinium Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Actinium Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02575963
First received: October 7, 2015
Last updated: August 28, 2017
Last verified: August 2017
  Purpose

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

  1. Establish the MTD of fractionated doses of Lintuzumab-Ac225 in combination with low dose cytosine arabinoside (Low Dose Ara-C, LDAC) (Phase 1 portion)
  2. Determine the response rate (CR + CRp + CRi) to fractionated doses of Lintuzumab-Ac225 alone (Phase 2 portion)

Condition Intervention Phase
AML Drug: Cytarabine (Phase 1 only) Biological: Lintuzumab-Ac225 Drug: Furosemide (Phase 1 only) Drug: Spironolactone Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of 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 ]
    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+CRi [ Time Frame: First evaluation at 42 days after treatment ]
    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 ]
    Progression Free Survival

  • Phase II: LFS [ Time Frame: 1 year ]
    Leukemia Free Survival

  • Phase II: OS [ Time Frame: 1 year ]
    Overall Survival

  • Phase II: Toxicity Spectrum [ Time Frame: 1 year ]

Estimated Enrollment: 72
Study Start Date: October 2012
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 (Completed)

Cytarabine + Lintuzumab-Ac225 Cytarabine days 1 to 10 of each cycle. Doses were 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. Furosemide (Phase 1 only) and Spironolactone were administered after Lintuzumab-Ac225.

Experimental: Phase 2

Experimental: Lintuzumab-Ac225 The Phase II dose determined during the Phase I dose escalation was 4.0 μCi/Kg Lintuzumab-Ac225 and 25 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given on Day 1 and the second fraction given on Day 5-8. Spironolactone is administered after Lintuzumab-Ac225.

Drug: Cytarabine (Phase 1 only)
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:
  • Low dose Ara-C
  • LDAC
Biological: Lintuzumab-Ac225
In Phase 1 the starting dose level was 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. In Phase 2 the dose will be 4.0 μCi/Kg Lintuzumab-Ac225 and 25 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given on Day 1 and the second fraction given on Day 5-8.
Other Names:
  • HuM195-Ac225
  • Actimab-A
Drug: Furosemide (Phase 1 only)
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 10 days after second dose of 225Ac-HuM195 and continued for 12 months.
Other Name: Aldactone

  Eligibility

Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Phase 1 Major 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

Phase 2 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. Patients ≥60 years unfit to receive intensive (e.g., 7+3) chemotherapy who have:

      • Congestive heart failure or documented cardiomyopathy with an EF ≤50%, provided that EF ≥35% or,
      • Documented pulmonary disease with DLCO ≤65% or FEV1 ≤65%, provided that patients do not require more than 2 L of oxygen per minute or,
      • Documented liver disease with marked elevation of transaminases >3 x ULN or,
      • Serum creatinine >1.2 mg/dL
    2. 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
    3. Any patient age ≥ 75 years.
  3. Blast count ≥ 20% (WHO criteria)
  4. Greater than 25% of blasts must be CD33 positive.
  5. Have a circulating blast count of less than 200/mm3 (control with hydroxyurea or similar agent is allowed);
  6. Creatinine < 2.0 mg/dl
  7. Estimated creatinine clearance ≥ 50ml/min
  8. Bilirubin ≤ 2.0 mg/dl; AST and ALT < 5.0 times the ULN
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 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. Patients with liver cirrhosis
  8. 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.
  9. 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 ClinicalTrials.gov identifier: NCT02575963

Contacts
Contact: Actinium Pharmaceuticals,Inc (Director of Clinical Operations) actimab@actiniumpharma.com

Locations
United States, California
UCLA Medical Center, Division of Hematology/Oncology Recruiting
Los Angeles, California, United States, 90095
United States, Kentucky
University of Kentucky, Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
United States, Louisiana
Ochsner Medical Center, The Gayle and Tom Benson Cancer Center Recruiting
New Orleans, Louisiana, United States, 70121
United States, New York
Weill Medical College of Cornell University Recruiting
New York, New York, United States, 10021
Columbia University Medical, Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, North Carolina
Duke Cancer Center Recruiting
Durham, North Carolina, United States, 27705
United States, Pennsylvania
University of Pennsylvania, Perelman Center for Advanced Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
St. Francis Cancer Center Recruiting
Greenville, South Carolina, United States, 29607
United States, Texas
Baylor Scott and White Research Institute, Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
United States, Washington
Swedish Cancer Institute, Center for Blood Disorders and Stem Cell Transplantation Recruiting
Seattle, Washington, United States, 98104
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
United States, West Virginia
West Virginia University, Mary Babb Randolph Cancer Center Recruiting
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Medical College of Wisconsin Cancer Center Recruiting
Milwaukee, Wisconsin, United States, 53226
Puerto Rico
VA Caribbean Healthcare System Recruiting
San Juan, Puerto Rico, 00921
Sponsors and Collaborators
Actinium Pharmaceuticals
Investigators
Study Director: Mark Berger, MD Actinium Pharmaceuticals Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Actinium Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02575963     History of Changes
Obsolete Identifiers: NCT01756677
Other Study ID Numbers: API-01
Study First Received: October 7, 2015
Last Updated: August 28, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antibodies, Monoclonal
Furosemide
Spironolactone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Diuretics
Natriuretic Agents
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing

ClinicalTrials.gov processed this record on September 21, 2017