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AMLPhase 1/2NCT02575963

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

A Phase 1/2 study testing Cytarabine (Phase 1 only), Lintuzumab-Ac225 and Furosemide (Phase 1 only) in people with AML, run by Actinium Pharmaceuticals at 17 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
AML
What is being tested?
Cytarabine (Phase 1 only), Lintuzumab-Ac225 and Furosemide (Phase 1 only)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
17 sitesin 2 countries
Study dates
Oct 2012to May 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • Patients with acute promyelocytic leukemia
  • Treatment with chemotherapy or biologic therapy within 3 weeks, except for hydroxyurea, which must be discontinued prior to treatment on study
  • Treatment with radiation within 6 weeks
  • Active serious infections uncontrolled by antibiotics
  • 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.
  • Clinically significant cardiac or pulmonary disease
Show all 9Show fewer
  • Patients with liver cirrhosis
  • 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.
  • Psychiatric disorder that would preclude study participation

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

United States16 sites
  • Baylor Scott and White Research Institute, Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Duke Cancer Center

    Durham, North Carolina, 27705

  • St. Francis Cancer Center

    Greenville, South Carolina, 29607

  • University of Kentucky, Markey Cancer Center

    Lexington, Kentucky, 40536

  • UCLA Medical Center, Division of Hematology/Oncology

    Los Angeles, California, 90095

  • University of Louisville, James Graham Brown Cancer Center

    Louisville, Kentucky, 40202

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • West Virginia University, Mary Babb Randolph Cancer Center

    Morgantown, West Virginia, 26506

  • Ochsner Medical Center, The Gayle and Tom Benson Cancer Center

    New Orleans, Louisiana, 70121

  • Weill Medical College of Cornell University

    New York, New York, 10021

  • Columbia University Medical, Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pennsylvania, Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Swedish Cancer Institute, Center for Blood Disorders and Stem Cell Transplantation

    Seattle, Washington, 98104

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

Other trials in United States

Puerto Rico1 site
  • VA Caribbean Healthcare System

    San Juan, 00921

Other trials in Puerto Rico

About this study

Official title: A Phase I/II Study of Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia

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)
Read the detailed description

The study is a multicenter, open label Phase I/II trial. Phase I, dose-escalation: This portion of the overall study uses a 3+3 design to estimate the maximum tolerated dose (MTD). The starting dose level will be 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 LDAC (20 mg subQ every 12 h x 10 days administered for cytoreduction) and the second fraction administered 4-7 days after the first fraction. Subjects will then go on to receive up to 11 additional cycles of LDAC or until progression of disease. Three to six patients will be treated at each dose level, and dose escalation will proceed if less than 33% of patients in a cohort experience dose-limiting toxicity.

Phase II, efficacy component. The study was designed as a 2- stage minimax design. Patients will be given two infusions of Lintuzumab-Ac225, 4-8 days apart (Day 5-Day 9), initially at the dose level determined to be the MTD in the Phase I portion. The second dose of Lintuzumab-Ac225 may be delayed up to 14 days after the first dose for clinical or scheduling reasons. Response will be initially assessed on or around days 28-42 after the final study drug administration. The primary endpoint (CR+CRp + CRi) will be determined on day 42. Best response will be evaluated from Day 1, Dose 1 until the end of the study.

Conditions
AML
Being tested
Cytarabine (Phase 1 only), Lintuzumab-Ac225, Furosemide (Phase 1 only), Spironolactone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cytarabine (Phase 1 only)Drug

    Also called Low dose Ara-C, LDAC

    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.

  • Lintuzumab-Ac225Biological

    Also called HuM195-Ac225, Actimab-A

    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.

  • Furosemide (Phase 1 only)Drug

    Also called 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.

  • SpironolactoneDrug

    Also called Aldactone

    25 mg by mouth daily, administered 10 days after second dose of 225Ac-HuM195 and continued for 12 months.

Study groups in NCT02575963
Study groupRoleWhat they receive
Phase 1 (Completed)ExperimentalCytarabine + 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.
Receives: Drug: Cytarabine (Phase 1 only); Biological: Lintuzumab-Ac225; Drug: Furosemide (Phase 1 only); Drug: Spironolactone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225

    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.

    Measured: Cycle 1, up to 52 days

  2. Phase II: CR+CRp+CRi

    The primary objective is to determine the antileukemic effects, including its ability to produce complete remissions, of Lintuzumab-Ac225.

    Measured: First evaluation at 42 days after treatment

Secondary outcomes (4)
  1. Phase II: PFS

    Progression Free Survival

    Measured: 1 year

  2. Phase II: LFS

    Leukemia Free Survival

    Measured: 1 year

  3. Phase II: OS

    Overall Survival

    Measured: 1 year

  4. Phase II: Toxicity Spectrum

    Safety Data

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2015 (estimated)
  2. Study startOct 2012
  3. Primary completionNov 2018
  4. Study completionMay 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02575963
Sponsor's protocol ID
API-01
Status last verified
Jul 2023
First submitted
7 Oct 2015
Last updated
20 Jul 2023
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Larson SM, Carrasquillo JA, Cheung NK, Press OW. Radioimmunotherapy of human tumours. Nat Rev Cancer. 2015 Jun;15(6):347-60. doi: 10.1038/nrc3925.

    PubMed 25998714
  • Jurcic JG, Rosenblat TL. Targeted alpha-particle immunotherapy for acute myeloid leukemia. Am Soc Clin Oncol Educ Book. 2014:e126-31. doi: 10.14694/EdBook_AM.2014.34.e126.

    PubMed 24857092
  • Scheinberg DA, McDevitt MR. Actinium-225 in targeted alpha-particle therapeutic applications. Curr Radiopharm. 2011 Oct;4(4):306-20. doi: 10.2174/1874471011104040306.

    PubMed 22202153
  • Nikitaki Z, Velalopoulou A, Zanni V, Tremi I, Havaki S, Kokkoris M, Gorgoulis VG, Koumenis C, Georgakilas AG. Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair. Expert Rev Mol Med. 2022 Mar 31;24:e15. doi: 10.1017/erm.2022.6.

    PubMed 35357290

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cytarabine (Phase 1 only), Lintuzumab-Ac225 and Furosemide (Phase 1 only) in people with AML, run by Actinium Pharmaceuticals at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 (time frame: Cycle 1, up to 52 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02575963, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.

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