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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 : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

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.


Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia (AML) Acute Lymphoblastic Leukemia (ALL) Myelodysplastic Syndromes (MDS) Lymphoma Myeloma Chronic Lymphocytic Leukemia (CLL) Chronic Myelogenous Leukemia (CML) Biological: ALT-803 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: IL-15 Super Agonist ALT-803 to Treat Relapse Of Hematologic Malignancy After Allogeneic Stem Cell Transplantation
Actual Study Start Date : November 11, 2013
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
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.
Biological: ALT-803
Given weekly IV at assigned dose level, ranging from 1mcg/kg to 30mcg/kg.




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. Incidence of acute graft versus host disease [ Time Frame: 100 days ]
  3. Incidence of chronic graft versus host disease [ Time Frame: 1 year ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01885897


Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Jeffrey S. Miller, MD Masonic Cancer Center, University of Minnesota

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01885897     History of Changes
Other Study ID Numbers: 2012LS023
HM2013-12 ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
First Posted: June 25, 2013    Key Record Dates
Last Update Posted: August 8, 2018
Last Verified: August 2018

Keywords provided by Masonic Cancer Center, University of Minnesota:
Acute myelogenous leukemia (AML)
Acute lymphoblastic leukemia (ALL)
Myelodysplastic syndromes (MDS)
Lymphoma
Myeloma
Chronic Lymphocytic Leukemia (CLL)
Chronic myelogenous leukemia (CML)

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Myeloproliferative Disorders