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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
Sponsor:
Information provided by (Responsible Party):
Actinium Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02575963
First received: October 7, 2015
Last updated: October 25, 2015
Last verified: October 2015

October 7, 2015
October 25, 2015
October 2012
January 2017   (final data collection date for primary outcome measure)
  • 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.
Same as current
Complete list of historical versions of study NCT02575963 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Phase II: Response Rate [ Time Frame: After 4, 28 day cycles ] [ Designated as safety issue: No ]
    Response criteria defined by Cheson et al. used. Patients assessed for response at the end of Cycle 4 (just prior to Cycle 5 LDAC administration). The response rate, complete remission plus complete remission with incomplete platelet count recovery (CR + CRp), is primary efficacy endpoint.
  • Phase II: PFS [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Progression Free Survival
Not Provided
Not Provided
 
Low Dose Cytarabine and Lintuzumab-Ac225 in Older AML Patients
A Phase I/II Study of Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia

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.

Phase I, dose-escalation component: A 3+3 study design to estimate the maximum tolerated dose (MTD). Total Lintuzumab-Ac225 dose will be administered as two equal fractionated doses. The first fraction will be administered administered approximately 4-7 days after the first ten-day cycle of LDAC is completed. The second fraction will be administered 4-7 days after the date of the first fraction. Up to 4 groups of up to 6 participants will be enrolled.

Phase II, efficacy component: A 2-stage minimax design is employed and will enroll up to 53 patients.

Study Groups:

If you are enrolled in the Phase I portion, the dose of Lintuzumab-Ac225 you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of Lintuzumab-Ac225. Each new group will receive a higher dose of Lintuzumab-Ac225 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of Lintuzumab-Ac225 is found.

If you are enrolled in the Phase II portion, you will receive Lintuzumab-Ac225 at the highest dose that was tolerated in the Phase I portion.

All participants will receive the same dose level of cytarabine.

Study Drug Administration:

You will receive cytarabine as an injection under the skin. This is called a subcutaneous injection. During the first office visit, you or a caregiver will be taught to give these injections at home. You will get cytarabine injections 2 times each day during Days 1-10 of each study cycle. Cycle 1 may last up to 52 days and will depend on how you recover from the Lintuzumab-Ac225. All other cycles will be 28 days.

You will receive Lintuzumab-Ac225 by vein over 15-30 minutes at a time point about 4 to 7 days after your last dose of cytarabine in Cycle 1. You will receive it a second time about 4 to 7 days after that.

One (1) day before the second dose of Lintuzumab-Ac225, you will begin taking lasix (furosemide) by mouth every day for 10 days. Furosemide is taken to prevent possible damage to the kidneys.

One (1) day after your last dose of furosemide, you will begin taking spironolactone by mouth every day for up to 1 year. It is also taken to prevent possible kidney damage.

You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks

Study Visits:

During Cycle 1:

  • Every week, blood (6-10 teaspoons) will be drawn for routine tests.
  • Every other week, urine will be collected for routine tests.
  • About 1 week before Cycle 2, you will have a bone marrow aspirate and biopsy to check the status of the disease.

During Cycles 2-12:

  • Every week, blood (6-10 teaspoons) will be drawn for routine tests.
  • Blood (about 1-2 teaspoons) will be drawn to find out how Lintuzumab-Ac225 may affect your immune system (Cycles 3, 4, and 7 only).
  • Every month, urine will be collected for routine tests.
  • About 1 week before Cycles 3 and 5, you will have a bone marrow aspirate and biopsy to check the status of the disease.

Length of Study:

You will only receive Lintuzumab-Ac225 during the first cycle, but you may continue receiving cytarabine for up to 12 cycles. You will be taken off the study if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the follow-up.

If you stop taking the study drugs before all 12 treatment cycles are finished, you may be contacted by telephone or be seen in the clinic every month for up to 1 year to check on any side effects you may be having.

This is an investigational study. Lintuzumab-Ac225 is not FDA approved or commercially available. It is currently being used for research purposes only. Cytarabine is FDA approved and commercially available for the treatment of AML. The use of these drugs in combination for AML is investigational.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
AML
  • 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
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.

Interventions:

  • Drug: Cytarabine
  • Biological: Lintuzumab-Ac225
  • Drug: Furosemide
  • Drug: Spironolactone
Interventions:
  • Drug: Cytarabine
  • Biological: Lintuzumab-Ac225
  • Drug: Furosemide
  • Drug: Spironolactone

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
72
May 2017
January 2017   (final data collection date for primary outcome measure)

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
Both
60 Years and older   (Adult, Senior)
No
Contact: Dragan Cicic, MD 646-459-4201 dcicic@actiniumpharmaceuticals.com
United States
 
NCT02575963
API-01
No
Not Provided
Not Provided
Actinium Pharmaceuticals
Actinium Pharmaceuticals
Not Provided
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
Actinium Pharmaceuticals
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP