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

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ClinicalTrials.gov Identifier: NCT01885897
Recruitment Status : Active, not recruiting
First Posted : June 25, 2013
Last Update Posted : September 26, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE June 11, 2013
First Posted Date  ICMJE June 25, 2013
Last Update Posted Date September 26, 2018
Actual Study Start Date  ICMJE November 11, 2013
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2013)
  • Dose Finding Phase: Safe dose of ALT-803 [ Time Frame: 4 weeks ]
    To establish a safe dose of ALT-803 given weekly for 4 doses in patients with hematologic malignancy who have relapsed after allogeneic transplant
  • Extended Phase: Efficacy of ALT-803 [ Time Frame: 4 months ]
    To study the potential efficacy of ALT-803 in this patient population as measured by the rates of remission induction
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01885897 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2013)
  • Number of patients with excessive toxicity. [ Time Frame: 4 weeks ]
    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.
  • Incidence of acute graft versus host disease [ Time Frame: 100 days ]
  • Incidence of chronic graft versus host disease [ Time Frame: 1 year ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic SCT
Official Title  ICMJE IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic Stem Cell Transplantation
Brief 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.

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myelogenous Leukemia (AML)
  • Acute Lymphoblastic Leukemia (ALL)
  • Myelodysplastic Syndromes (MDS)
  • Lymphoma
  • Myeloma
  • Chronic Lymphocytic Leukemia (CLL)
  • Chronic Myelogenous Leukemia (CML)
Intervention  ICMJE Biological: ALT-803
Given weekly IV at assigned dose level, ranging from 1mcg/kg to 30mcg/kg.
Study Arms Experimental: Study treatment
Weekly 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.
Intervention: Biological: ALT-803
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 21, 2013)
61
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date June 2020
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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)
  • 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)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01885897
Other Study ID Numbers  ICMJE 2012LS023
HM2013-12 ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey S. Miller, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date September 2018

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