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Acute Myeloid LeukemiaPhase 1NCT03705858

Actinium-225-Lintuzumab in Patients With Acute Myeloid Leukemia

A Phase 1 study testing Ac-Lintuzumab in people with Acute Myeloid Leukemia, run by Joseph Jurcic.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to see what dose of 225Ac-lintuzumab is safest to give to acute myeloid leukemia (AML) patients who are in remission but still have minimal residual disease (MRD). About 12 subjects will be asked to take part in this phase 1, 3+3 dose-escalation study. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Ac-Lintuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
28 Feb 2019to 28 Feb 2019
Phase
Phase 1
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 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must have histologically confirmed AML in first, second, or third clinical CR/CRp after any standard or investigational therapy.
  • Subjects must have detectable MRD by cytogenetics, FISH, or flow cytometry after the completion of all planned therapy. Detectable MRD by flow cytometry is defined by the presence of a myeloid blast population with an atypical immunophenotype, constituting less than 5% of all events. Examples of planned therapy courses include induction chemotherapy with cytarabine and an anthracycline followed by consolidation chemotherapy or 4-6 cycles of a hypomethylating agent-based regimen.
  • At the time of diagnosis or most recent relapse, greater than 25% of bone marrow blasts must have been CD33 positive.
  • Age ≥18 years. Because no dosing or adverse event data are currently available on the use of 225Ac-lintuzumab in patients <18 years of age, children are excluded from this study.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Subjects must have adequate bone marrow and organ function documented within 14 days of study entry as follows:
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  • Absolute neutrophil count (ANC) ≥ 1,000/μL;
  • Platelet count ≥ 50,000/μL;
  • Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or estimated glomerular filtration rate of > 50 mL/min;
  • Serum total bilirubin ≤ 1.5 × ULN (unless attributable to Gilbert's disease);
  • Alkaline phosphatase, serum aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT) ≤ 2.5 × ULN.
  • The effects of 225Ac-lintuzumab on the developing human fetus are unknown. Since radiation exposure, however, is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of treatment on study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of 225Ac-lintuzumab administration.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Subjects with acute promyelocytic leukemia or BCR-ABL-positive leukemia.
  • Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Prior clofarabine is not allowed due to risk of liver dysfunction.
  • Subjects who have previously received 225Ac-lintuzumab.
  • Subjects with an human leukocyte antigen (HLA)-compatible donor or stem cell source who are immediate candidates for allogeneic hematopoietic cell transplantation (HCT).
  • Subjects who are receiving any other investigational agents concurrently.
  • Subjects with active central nervous system (CNS) involvement by AML.
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  • Uncontrolled intercurrent illness including, but not limited to, active serious infections uncontrolled by antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, documented liver cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Active malignancy within 3 years of study entry, except previously treated melanoma grade 2 or less, non-melanoma skin cancer, carcinoma in situ or cervical intraepithelial neoplasia, and organ confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) levels and are not on active therapy.
  • Prior organ transplant, including allogeneic HCT.
  • Pregnant or nursing women.
  • Subjects with known human immunodeficiency virus (HIV) infection, active hepatitis B, or active hepatitis C.

About this study

Official title: Postremission Therapy With Actinium-225 (225Ac)-Lintuzumab (Actimab-A®) in Patients With Acute Myeloid Leukemia

The purpose of this study is to see what dose of 225Ac-lintuzumab is safest to give to acute myeloid leukemia (AML) patients who are in remission but still have minimal residual disease (MRD). About 12 subjects will be asked to take part in this phase 1, 3+3 dose-escalation study. In addition to confirming the safety profile of postremission therapy with 225Ac-lintuzumab, preliminary evidence of efficacy will be assessed by estimating progression-free survival (PFS) and overall survival (OS), and serially evaluating for MRD using cytogenetics, fluorescence in situ hybridization (FISH), or flow cytometric assays, as applicable.

Read the detailed description

Therapy with α particle-emitting constructs of the anti-CD33 monoclonal antibody lintuzumab has demonstrated significant tumor effects in AML. Because therapy is selectively targeted to leukemic blasts, it has the potential advantage of less extramedullary toxicity than conventional systemic agents. Moreover, the unique radiobiological features of α particle emissions may permit more efficient tumor cell kill with greater specificity than treatment with β particle-emitting radioisotopes. Objective responses in AML following treatment with 225Ac-lintuzumab have been seen in cytoreduced disease, either following chemotherapy or using a fractionated dosing scheme.

The presence of MRD detectable by cytogenetic techniques and flow cytometric assays indicates a high risk of relapse for AML patients, despite achieving a clinical complete remission. The high linear energy and short range of α emissions make them ideally suited to eradicate MRD, as suggested by the clinical responses observed in earlier studies. To date, 225Ac-lintuzumab has only been studied in patients with overt leukemia. The aim of this phase 1 study is to identify the maximum tolerated dose (MTD) of 225Ac-lintuzumab that can be given safely to AML patients in the postremission setting in order to eliminate detectable MRD and ultimately prolong PFS and OS.

Being tested
Ac-Lintuzumab
Keywords
Acute Myeloid Leukemia, Actinium-225, Lintuzumab, Columbia, Post-remission, Phase I
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • Ac-LintuzumabDrug

    Also called Actimab-A ®

    225Ac-lintuzumab will administered at 4 dose levels: 0.25, 0.5, 0.75 or 1 µCi/kg intravenously (IV) over 30 ± 10 minutes. The starting dose will be 0.5 µCi/kg. A dose of 0.25 µCi/kg will be studied only if 0.5 µCi/kg is determined to exceed the MTD. The lintuzumab dose will be adjusted to maintain a specific activity of 0.16 µCi/µg

Study groups in NCT03705858
Study groupRoleWhat they receive
Ac-lintuzumabExperimentalSubjects with AML will receive Ac-lintuzumab.
Receives: Drug: Ac-Lintuzumab

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of postremission therapy

    The 3+3 dose-escalation is designed to establish the MTD of postremission therapy with 225Ac-lintuzumab in patients with AML in first, second, or third CR/CRp who have detectable minimal residual disease (MRD) and have completed all planned therapy.

    Measured: Up to 2 years

Secondary outcomes (2)

  1. Progression Free Survival (PFS)

    The length of time during and after the treatment of AML that a subject lives with the disease but it does not get worse. It will be calculated from the time of study entry to relapse, death or last follow-up. That includes subjects with at least one cycle of therapy.

    Measured: Up to 3 years

  2. Overall Survival (OS)

    The Length of time in days during and after the treatment of AML that a subject lives. It will be calculated from the time of entry onto study to death or last follow-up. That includes all subjects who receive at least one cycle of therapy.

    Measured: Up to 3 years

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 2018
  2. Study start28 Feb 2019
  3. Primary completion28 Feb 2019
  4. Study completion28 Feb 2019

Why it stopped: Due to difficulty in finalizing the contract

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03705858
Sponsor's protocol ID
AAAR9075
Status last verified
Mar 2019
First submitted
10 Oct 2018
Last updated
8 Mar 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ac-Lintuzumab in people with Acute Myeloid Leukemia, run by Joseph Jurcic.

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 13 inclusion and 11 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: withdrawn, as of the sponsor's last update on 8 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

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 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.

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 was withdrawn before enrolling participants, so there are no results.

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?

Maximum Tolerated Dose (MTD) of postremission therapy (time frame: Up to 2 years). 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 NCT03705858.

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 8 Mar 2019.

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