AzTrials
AzTrials

Acute Myelogenous Leukemia (AML)Phase 1/2NCT01885897

IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic SCT

A Phase 1/2 study testing ALT-803 in people with Acute Myelogenous Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), run by Masonic Cancer Center, University of Minnesota at 3 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

This is a multi-center, phase I/II clinical trial for patients who have relapsed more than 60 day after allogeneic transplant for a hematologic malignancy. The study consists of two phases. The dose finding phase is a modified version of a phase I trial and the extended phase is a modified version of a phase II trial. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ALT-803
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
3 sitesUnited States
Study dates
11 Nov 2013to Jul 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • Relapse after previous allogeneic stem cell transplant for one of the following hematologic malignancies (acute myelogenous leukemia, acute lymphoblastic leukemia,myelodysplastic syndromes, lymphoma, myeloma, Chronic lymphocytic Leukemia, chronic myelogenous leukemia):
  • For non-CML, relapse will be defined based on disease specific morphologic criteria from a bone marrow biopsy and aspirate or recurrence of disease specific cytogenetics. For disease specific definition of relapse, see appendix III. Relapse can be determined morphologically. Equivocal results for relapse should result in a repeated test after an appropriate time interval (suggested 1 month) to determine eligibility.
  • For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least two measurements over a 6 month interval. If cytogenetics are normal and there is PCR evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of a quantitative increase in CML measured either by quantitative PCR or by fluorescent in situ hybridization (FISH).
  • For Chronic Phase CML patients only:
  • must have failed (no response in 3 months or incomplete response at 6 months) or refused treatment with a tyrosine-kinase inhibitor (TKI)
  • must have failed (defined as incomplete response or relapse) or refused DLI
Show all 21Show fewer
  • Relapse must have occurred ≥ 60 days after transplant
  • Prior DLI is allowed, however not within the 30 days before the 1st dose of ALT-803
  • Minimum donor chimerism of 10%
  • ≥ 18 years of age
  • Karnofsky performance status ≥ 70% (appendix II)
  • Adequate organ function within 14 days (30 days for cardiac and pulmonary) of enrollment defined as:
  • Creatinine: ≤ 2.0 mg/dL
  • Hepatic: SGOT/SGPT < 5 x upper limit of institutional normal (ULN)
  • Thyroid Function: Thyroid Stimulating Hormone (TSH) within institutional normal range - patients with thyroid disease are eligible if euthyroid on suppressive or replacement therapy
  • Pulmonary: PFTs > 50% of predicted
  • Cardiac: LVEF by ECHO or MUGA > 40%
  • Ability to be off prednisone and other immunosuppressive drugs for at least 30 day before first dose of study drug
  • Patient agrees to stay within a reasonable distance (i.e. 30 miles) of the study site for the duration of the study treatment and for a minimum of 48 hours after the last dose and has a dedicated care giver as is standard practice for BMT outpatient care
  • Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy
  • Voluntary written consent

Who cannot join

  • Post-transplant lymphoproliferative diseases (often referred to as EBV-associated lymphomas)
  • Known active CNS leukemia or lymphoma - patients with previously treated CNS disease is permitted if neurologically stable with no ongoing or anticipated need for steroid therapy are eligible
  • Ongoing active acute or chronic GVHD requiring immunosuppressive therapy or signs of aGVHD or cGVHD requiring treatment
  • Pregnant or lactating - Women of child bearing potential must have a negative pregnancy test within 14 days of study treatment start
  • Class II or greater New York Heart Association Functional Classification criteria (appendix II) or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy
  • Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
Show all 11Show fewer
  • New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan for which evaluation with bronchoscopy is not feasible. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
  • Active bacterial, fungal, or viral infections - all prior infections must have resolved following optimal therapy
  • Positive hepatitis C serology or active hepatitis B infection because of the risk of hepatic inflammation and the possible confounding of drug toxicity assessment - chronic asymptomatic viral hepatitis is allowed
  • HIV positive because the effect of IL-15 viral loads, HIV immunity, and infectivity of proliferating T cells is unknown
  • History of severe asthma, presently on chronic medications (a history of mild asthma not requiring therapy is eligible)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic Stem Cell Transplantation

This is a multi-center, phase I/II clinical trial for patients who have relapsed more than 60 day after allogeneic transplant for a hematologic malignancy. The study consists of two phases. The dose finding phase is a modified version of a phase I trial and the extended phase is a modified version of a phase II trial.

The primary objective of the dose finding phase is to determine the maximum tolerated, minimum efficacious dose (MTD/MED) of a interleukin-15 (IL-15) super agonist complex (ALT-803) when given once weekly for 4 weeks in the outpatient setting. The study will follow a standard 3+3 design of dose escalation for toxicity with an added feature of stopping early if efficacy is confirmed. There are six dose levels of ALT-803 for to determine the MTD/MED: 1, 3, 6, 10, 20, and 30 mcg/kg.

Once the MTD/MED for ALT-803 is determined, this cohort will be used in the extended phase. The primary goal of this extended phase is to study the potential efficacy of ALT-803 in this patient population. Efficacy will be measured using rates of remission induction. An optimal Simon's two-stage design will be used in this phase. Stage 1 will enroll 14 patients (including the 6 patients treated at the MTD/MED during the dose finding phase). If 3 or more of these 14 patients respond to ALT-803, the trial will move to stage 2 and enroll an additional 23 patients. If 2 or fewer respond, the study will terminate enrollment early.

Being tested
ALT-803
Keywords
Acute myelogenous leukemia (AML), Acute lymphoblastic leukemia (ALL), Myelodysplastic syndromes (MDS), Lymphoma, Myeloma, Chronic Lymphocytic Leukemia (CLL), Chronic myelogenous leukemia (CML)
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Lymphoma, Neoplasms, Plasma Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

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

  • ALT-803Biological

    Given weekly IV at assigned dose level, ranging from 1mcg/kg to 30mcg/kg.

Study groups in NCT01885897
Study groupRoleWhat they receive
Study treatmentExperimentalWeekly dose of ALT-803 at assigned dose, ranging from 1mcg/kg to 30 mcg/kg (based on phase 1 dose escalation schedule,) IV once a week for 4 weeks.
Receives: Biological: ALT-803

What is being measured

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

  1. Number of Participants With Dose Limiting Toxicity (DLT) Events

    The Dose Limiting Toxicity (DLT) is defined as (during first treatment cycle only):

    • any treatment-emergent grade 3 non-hematologic toxicity lasting more than 48 hours (refer to section 6.2.1.1 for full definition)
    • any treatment-emergent grade 4 or 5 non-hematologic toxicity of any duration
    • grade III or IV acute GVHD within 6 weeks after the first ALT-803 dose Maximum Tolerated Dose (MTD) is defined as the dose level where ≤ 1 out of 6 patients has DLT during the first treatment cycle

    Measured: 4 weeks

  2. Number of Participants Experiencing Potential Efficacy of ALT 803

    The potential efficacy of ALT-803 in this patient population is measured by the responses based on bone marrow examination 1 and 3 months after the last dose of ALT-803.

    Response was defined as follows: for AML and myelodysplastic syndromes (MDS) using the International Working Group modified criteria, non-Hodgkin lymphoma, and multiple myeloma using the International Myeloma Working Group Uniform Response Criteria, and acute lymphoblastic leukemia using protocol-specified criteria.

    Measured: 4 months

Secondary outcomes (3)

  1. Number of Participants With Excessive Toxicity

    To evaluate the safety of the ALT-803 when administered on this schedule. Excessive toxicity is defined as having a grade 3-5 non-hematologic, non-relapse and non-infectious toxicity (except fevers alone) based on the NCI's CTCAE version 4.

    Measured: 4 weeks

  2. Number of Participants With Incidence of Acute Graft Versus Host Disease

    Measured: 100 days

  3. Number of Participants With Incidence of Chronic Graft Versus Host Disease

    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 posted25 Jun 2013 (estimated)
  2. Study start11 Nov 2013
  3. Primary completionJul 2019
  4. Study completionJul 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
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01885897
Sponsor's protocol ID
2012LS023
Other IDs
HM2013-12
Status last verified
Jul 2020
First submitted
11 Jun 2013
Last updated
12 Aug 2020
Data monitoring committee
Yes

Publications

  • Romee R, Cooley S, Berrien-Elliott MM, Westervelt P, Verneris MR, Wagner JE, Weisdorf DJ, Blazar BR, Ustun C, DeFor TE, Vivek S, Peck L, DiPersio JF, Cashen AF, Kyllo R, Musiek A, Schaffer A, Anadkat MJ, Rosman I, Miller D, Egan JO, Jeng EK, Rock A, Wong HC, Fehniger TA, Miller JS. First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation. Blood. 2018 Jun 7;131(23):2515-2527. doi: 10.1182/blood-2017-12-823757. Epub 2018 Feb 20.

    PubMed 29463563

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ALT-803 in people with Acute Myelogenous Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), run by Masonic Cancer Center, University of Minnesota at 3 sites in United States.

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 21 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: finished, as of the sponsor's last update on 12 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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?

Yes. Results are posted in the registry (first posted 12 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Dose Limiting Toxicity (DLT) Events (time frame: 4 weeks). 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 NCT01885897, which also lists 1 linked publication.

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 12 Aug 2020; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in