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QUILT-3.002: ALT-803 in Patients With Relapse/Refractory iNHL in Conjunction With Rituximab

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ClinicalTrials.gov Identifier: NCT02384954
Recruitment Status : Recruiting
First Posted : March 10, 2015
Last Update Posted : May 8, 2018
Sponsor:
Information provided by (Responsible Party):
Altor BioScience

Brief Summary:
This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of ALT-803 in patients with relapse/refractory indolent B cell non-Hodgkin lymphoma in conjunction with rituximab.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Indolent B Cell Non-Hodgkin Lymphoma Biological: Rituximab Biological: ALT-803 Phase 1 Phase 2

Detailed Description:

The purpose of this study is to evaluate the safety and tolerability, identify the Maximum Tolerated Dose (MTD) or the Minimum Efficacious Dose (MED) and designate a dose level for Phase 2. Also characterize the immunogenicity, pharmacokinetic profile, and biomarker serum levels of ALT-803 in treated patients.

The effect of ALT-803 on the peripheral absolute lymphocyte counts and white blood cell counts, the number, phenotype and repertoire of peripheral blood T (total and subsets) and NK cells will be evaluated. In addition, a subset of patients will be evaluated for changes in lymph node immune composition. Anti-tumor responses and survival data will also be collected in this trial.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of ALT-803 in Patients With Relapse/Refractory Indolent B Cell Non-Hodgkin Lymphoma in Conjunction With Rituximab
Actual Study Start Date : April 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Phase I/II ALT-803 w/rituximab for rel/ref iNHL Biological: Rituximab
Intravenous infusion; Patients will receive a 4-week induction cycle consisting of Rituximab given on Day 1, 8, 15, 22. Eligible patients will receive a consolidation treatment consisting of Rituximab given on Day 78, 134, 190, 246.
Other Name: Rituxin
Biological: ALT-803
Intravenous infusion for cohort 1, 2 and 3; subcutaneous injection for cohort 4, 5, 6 and 7; Patients will receive a 4-week induction cycle consisting of ALT-803 given on Day 2, 8, 15, 22 for patients in cohort 1, 2, 3, 4 and Day 1, 8, 15 and 22 for patients in cohort 5, 6, 7. Eligible patients will receive a consolidation treatment consisting of ALT-803 given on Day 78, 134, 190, 246.



Primary Outcome Measures :
  1. Determination of MTD or MED, Phase II Dose Level Designation [ Time Frame: 9 months ]

    For Phase I

    Determine the maximum tolerated dose (MTD) level or minimum efficacious dose (MED) and designate the dose level for phase II.


  2. Number of treatment related adverse events as a measure of safety [ Time Frame: 36 months ]

    For Phase 1 and 2

    Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment will be collected.


  3. Overall Response Rate [ Time Frame: 60 months ]

    For Phase 1 and 2

    Complete response plus partial response of treated patients



Secondary Outcome Measures :
  1. Progression-free Survival [ Time Frame: 60 months ]

    For Phase 1 and 2

    Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).


  2. Overall Survival [ Time Frame: 60 months ]

    For Phase 1 and 2

    Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).


  3. Duration of Response [ Time Frame: 60 months ]

    For Phase 1 and 2

    Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).


  4. Blood Cell Counts [ Time Frame: 36 months ]

    For Phase 1 and 2

    Evaluation of the effect of ALT-803 on the peripheral ALC and WBC counts, the number and phenotype of peripheral blood T (total and subsets) and NK cells in treated patients.


  5. Levels of specific biomarkers as a predictive measure of efficacy [ Time Frame: 36 Months ]
    For Phase 1 and 2 Measures the serum levels of including but not limited to IL-2, IL-4, IL-6, IL-10, IFN-gamma, MCP-1 and TNF-alpha in treated patients.

  6. Immunogenicity [ Time Frame: 36 Months ]

    For Phase 1 and 2

    Measure the level of anti-ALT-803 neutralizing effects in each patient


  7. Pharmacokinetics as a measure of drug persistence [ Time Frame: 36 Months ]

    For Phase 1 and 2

    Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-803 collected from treated patients.


  8. Polymorphism [ Time Frame: 36 Months ]

    For Phase 1 and 2

    Determine the fcgr3a polymorphism status in each patient to correlate with clinical outcomes.


  9. Mutations [ Time Frame: 36 Months ]

    For Phase 1 and 2

    Test the recurrent lymphoma mutations in each patient to correlate with clinical outcomes.


  10. Lymph node biopsies [ Time Frame: 36 Months ]

    For Phase 1 and 2

    Determine the impact of study treatment on the immune cell composition within the tumor microenvironment.




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

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of iNHL (Follicular lymphoma grade 1, 2, 3a; marginal zone lymphoma; small lymphocytic lymphoma or lymphoplasmacytic lymphoma) after treatment with at least 1 or more prior rituximab-containing regimens.

    • Anti-CD20 mAb-refractory disease is defined as progressive disease while on rituximab (or another treatment of an anti-CD20 monoclonal antibody) or progression within 6 months of rituximab-containing (or another treatment of an anti-CD20 antibody-containing) therapy.
    • Anti-CD20 mAb-sensitive disease is defined by a response to a prior rituximab-containing (or another treatment of an anti-CD20 monoclonal antibody) regimen, and relapse more than 6 months from the last administration of rituximab-containing (or another treatment of an anti-CD20 antibody-containing) therapy.
  • Measurable disease:

    • At least one lymph node group ≥ 1.5 cm in longest transverse dimension. Patients with cutaneous only disease may be enrolled if they have a clearly measurable skin lesion.
    • Relapsed or Refractory iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment of an anti-CD20 antibody-containing) regimens for lymphoma

PRIOR/CONCURRENT THERAPY:

  • No anti-lymphoma treatments within 28 days before the start of study treatment.
  • Must have recovered from side effects of prior treatments.

PATIENT CHARACTERISTICS:

Performance Status

• ECOG 0, 1, or 2

Renal Function • Glomerular Filtration Rate (GFR) > 40mL/min or Serum creatinine ≤ 1.5 X ULN

Bone Marrow Reserve

  • Platelets ≥30,000/uL
  • Hemoglobin ≥ 8g/dL
  • Absolute Lymphocytes ≥800/uL
  • ANC/AGC ≥750/uL

Hepatic Function

  • Total bilirubin ≤ 2.0 X ULN (unless Gilbert's Syndrome or disease infiltration of liver is present)
  • AST, ALT ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver lymphoma is present)
  • No positive Hep C serology or active Hep B infection

Cardiovascular

  • No congestive heart failure < 6 months
  • No unstable angina pectoris < 6 months
  • No myocardial infarction < 6 months
  • No history of ventricular arrhythmias or severe cardiac dysfunction
  • No history of uncontrollable supraventricular arrhythmias
  • No NYHA Class > II CHF
  • No marked baseline prolongation of QT/QTc interval

Pulmonary

• Normal clinical assessment of pulmonary function

Other

  • Negative serum pregnancy test if female and of childbearing potential
  • Women who are not pregnant or nursing
  • Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
  • No known autoimmune disease other than corrected hypothyroidism
  • No known prior organ allograft or allogeneic transplantation
  • Not HIV positive
  • No active CNS involvement with lymphoma
  • No psychiatric illness/social situation that would limit compliance
  • No other illness that in the opinion of the investigator would exclude the subject from participating in the study
  • Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
  • No active systemic infection requiring parenteral antibiotic therapy
  • No disease requiring systemic immunosuppressive therapy (inhaled or topical steroids are allowed). Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
  • No known histologic transformation from iNHL to DLBCL

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): NCT02384954


Contacts
Contact: Kyle Conradi 9544438600 kyleconradi@altorbioscience.com
Contact: Liza Hernandez 9544438600 lizahernandez@altorbioscience.com

Locations
United States, Minnesota
University of Minnesota Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: JoAnn Knox    612-624-9489    knox001@umn.edu   
Principal Investigator: Veronika Bachanova, MD, PhD         
United States, Missouri
Washington University School of Medicine Oncology Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Kristen McDaniels    314-747-1207    k.mcdaniels@wustl.edu   
Principal Investigator: Todd A Fehniger, M.D., Ph.D.         
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Raoof Giali    614-688-7313    Raoof.Giali@osumc.edu   
Principal Investigator: Narendranath Epperla, MD         
United States, Pennsylvania
Thomas Jefferson University Withdrawn
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Ashley Billanti    843-792-8856    billanti@musc.edu   
Principal Investigator: Valeriy Sedov, MD         
Sponsors and Collaborators
Altor BioScience

Responsible Party: Altor BioScience
ClinicalTrials.gov Identifier: NCT02384954     History of Changes
Other Study ID Numbers: CA-ALT-803-02-14
First Posted: March 10, 2015    Key Record Dates
Last Update Posted: May 8, 2018
Last Verified: May 2018

Keywords provided by Altor BioScience:
Lymphoma
indolent B Cell
non-Hodgkin Lymphoma
Cancer
Immunotherapy
Relapsed
Refractory
Rituximab
Interleukin-15
Absolute Lymphocyte Count
White Blood Cell
Follicular Lymphoma
Marginal Zone Lymphoma
Small Lymphocytic Lymphoma
Lymphoplasmacytic Lymphoma
anti-CD20

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents