Clinical Trials /

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

NCT01885897

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2012LS023
  • SECONDARY ID: HM2013-12
  • NCT ID: NCT01885897

Conditions

  • Acute Myelogenous Leukemia (AML)
  • Acute Lymphoblastic Leukemia (ALL)
  • Myelodysplastic Syndromes (MDS)
  • Lymphoma
  • Myeloma
  • Chronic Lymphocytic Leukemia (CLL)
  • Chronic Myelogenous Leukemia (CML)

Interventions

DrugSynonymsArms
ALT-803Study treatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
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.

    Eligibility Criteria

            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)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Dose Finding Phase: Safe dose of ALT-803
    Time Frame:4 weeks
    Safety Issue:
    Description:To establish a safe dose of ALT-803 given weekly for 4 doses in patients with hematologic malignancy who have relapsed after allogeneic transplant

    Secondary Outcome Measures

    Measure:Number of patients with excessive toxicity.
    Time Frame:4 weeks
    Safety Issue:
    Description: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.
    Measure:Incidence of acute graft versus host disease
    Time Frame:100 days
    Safety Issue:
    Description:
    Measure:Incidence of chronic graft versus host disease
    Time Frame:1 year
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:Masonic Cancer Center, University of Minnesota

    Trial Keywords

    • Acute myelogenous leukemia (AML)
    • Acute lymphoblastic leukemia (ALL)
    • Myelodysplastic syndromes (MDS)
    • Lymphoma
    • Myeloma
    • Chronic Lymphocytic Leukemia (CLL)
    • Chronic myelogenous leukemia (CML)

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