QUILT-3.005: A Study of ALT-803 in Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of ALT-803 in patients with relapsed or refractory multiple myeloma.

Detailed Description
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The purpose of this study is to evaluate the safety, determine the Maximum Tolerated Dose (MTD) or the Minimum Efficacious Dose (MED) and characterize the immunogenicity and pharmacokinetic profile of ALT-803 in treated patients. The effect of ALT-803 on the peripheral absolute lymphocyte counts and white blood cell counts, the number and phenotype of peripheral blood T (total and subsets) and NK cells will be evaluated. The anti-tumor responses of ALT-803 will also be assessed in this trial.

Official Title
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A Phase I/II Study of ALT-803 in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: ALT-803


Participation Criteria
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Eligibility Criteria
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ENTRY CRITERIA: DISEASE CHARACTERISTICS: Confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at least two different previous regimens. Refractory disease is defined as progressive disease while on therapy or progression within 60 days of therapy. Progressive disease is defined by a 25% increase from the lowest response value in specified tests. Measurable disease as defined by at least one of the following: Serum M-protein ≥ 1g/dL (for IgG, IgM) or 0.5 g/dL (for IgA) Urine M-protein ≥ 200mg/24hours Serum free light chains ≥ 10 mg/dL and abnormal kappa/lambda ratio PRIOR/CONCURRENT THERAPY: No anti-myeloma treatments within 14 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 Bone Marrow Reserve Absolute neutrophil count (AGC/ANC) ≥ 1000/uL Platelets ≥ 30,000/uL Hemoglobin ≥ 8g/dL Absolute lymphocytes ≥ 800/uL Leukocytes ≥ 3,000/uL Renal Function • Glomerular Filtration Rate (GFR) > 40mL/min or Serum creatinine ≤ 1.5 X ULN Hepatic Function Total bilirubin ≤ 2.0 X ULN AST, ALT, ALP ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver metastases exist) 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 No history of 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 history or evidence of uncontrollable CNS disease No psychiatric illness/social situation 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 on-going chronic systemic corticosteroid (>10 mg daily prednisone equivalent) use or other immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALT-803<br> | Biological: ALT-803<br>* Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile | For phase I & II Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment. | 24 months | 
| MTD or MED Determination, Phase II Dose Level Designation | For phase I only Determine the maximum tolerated dose (MTD) level or minimum efficacious dose (MED) and designate the dose level for phase II. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit | For phase I and II Number of participants with an objective response, which includes, a complete response, a partial response or a stable disease. | 24 months | 
| Blood Cell Counts | For phase Ib and II 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. | 24 months | 
| Pharmacokinetics | For phase I and II Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-803. | 24 months | 
| Biomarkers | For phase I and II Measures the serum levels of IL-2, IL-4, IL-6, IL-10, IFN-gamma, MCP-1 and TNF-alpha in treated patients. | 24 months | 
| Immunogenicity | For Phase I and II Measures the anti-ALT-803 neutralizing effects. | 24 months | 
| Overall Survival | All enrolled patients will be assessed every 3 months during year 1 and then every 6 months during years 2 and 3 from the start of study treatment to determine their overall survival, progression-free survival and duration of response. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory, absolute lymphocyte count, antitumor, cancer, immunotherapy, immunochemotherapy, interleukin-15, NK cell, multiple myeloma, relapsed, T cell, white blood cell count