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

Relapsed or Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02099539
• Other study ID #: CA-ALT-803-02-13
• Secondary ID: CA167925
• Status: Active, not recruiting
• Phase: Phase 1
• First received: February 26, 2014
• Last updated: January 19, 2018
• Start date: October 2014
• Est. completion date: October 2020

Study information

• Verified date: January 2018
• Source: Altor BioScience
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: October 2020
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Biological:
• ALT-803
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

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Altor BioScience	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Immunogenicity	For Phase I and II; Measures the anti-ALT-803 neutralizing effects.	24 months
Secondary	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