Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients

This study is currently recruiting participants.
Verified February 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Actinium Pharmaceuticals
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01756677
First received: December 20, 2012
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

The goal of the Phase 1 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 2 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
Leukemia
Drug: Cytarabine
Biological: Lintuzumab-Ac225
Drug: Lasix
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 M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 [ Time Frame: Cycle 1, up to 52 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: October 2012
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cytarabine + Lintuzumab-Ac225
Cytarabine 20 mg subcutaneously every 12 hours Days 1 to 10 of every cycle. 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. Lasix 40 mg by mouth (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, administered 11 days after second dose of 225Ac-HuM195 (the day after completion of furosemide) and continued for 12 months.
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 Name: Lintuzumab
Drug: Lasix
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: furosemide
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Untreated acute myelogenous leukemia (AML), including patients with an antecedent hematologic disorder or secondary disease. Patients with prior myelodysplastic syndromes (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 ahve no measurable disease are not undergoing active therapy, and have a life expectancy of greater than or equal 4 months.
  2. Patients age greater than or equal to 60 years who: a. Are unwilling to receive intensive (e.g. 7+3) chemotherapy, or b. Have poor-risk prognostic factors defined as antecedent hematologic disorder, prior chemotherapy or chemoradiation therapy (XRT), abnormal karyotype other than t(8;21), inv16, or t(16;16), any karyotype with Internal tandem duplications of Flt3 (Flt3-ITD), or presenting white blood count (WBC) greater than 100K, or c. 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 d. Any patient age greater than or equal to 70 years.
  3. Blast count greater than or equal to 20 percent (World Health Organization (WHO) criteria)
  4. Greater than 25 percent of blasts must be CD33 positive.
  5. Creatinine less than 2.0 mg/dl
  6. Estimated creatinine clearance greater than or equal to 50ml/min.
  7. Bilirubin less than or equal to 2.0 mg/dl; aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) less than or equal to 2.5 times the upper limits of normal (ULN).
  8. Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 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 prostate-specific antigen (PSA) levels and are not on active therapy
  6. Clinically significant cardiac or pulmonary disease
  7. Active central nervous system (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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01756677

Contacts
Contact: Farhad Ravandi-Kashani, MD 713-745-0394

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Farhad Ravandi-Kashani, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Actinium Pharmaceuticals
Investigators
Study Chair: Farhad Ravandi-Kashani, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01756677     History of Changes
Other Study ID Numbers: 2012-0434, API-01
Study First Received: December 20, 2012
Last Updated: February 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Cytarabine
Lintuzumab-Ac225
ACTINIUM-225
HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195
Alpha-Particle-Emitting Immunoconjugates

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

ClinicalTrials.gov processed this record on April 15, 2014