QUILT-2.001: ALT-803 In Patients With Advanced Pancreatic Cancer In Conjunction With Gemcitabine And Nab-Paclitaxel

Study Overview

QUILT-2.001: ALT-803 in Patients With Advanced Pancreatic Cancer in Conjunction With Gemcitabine and Nab-Paclitaxel

This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose escalation study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer in conjunction with gemcitabine and nab-paclitaxel.

The purpose of this study is to evaluate the safety and tolerability of escalating doses, to identify the Maximum Tolerated Dose (MTD) and designate a dose level for Phase II study (RP2D) of ALT-803 administered in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. To access the anti-tumor activity of ALT-803 administered in combination with gemcitabine and nab-paclitaxel as measured by objective response rate, overall survival, progression-free survival, time to progression, and duration of response in patients with advanced pancreatic cancer. To Characterize the pharmacokinetic, immunogenicity, and serum cytokine profile of ALT-803 in combination with gemcitabine and nab-paclitaxel in treated patients. To correlate circulating cell free DNA and circulating tumor DNA with clinical outcomes of the study in treated patients.

Advanced Pancreatic Cancer

BIOLOGICAL: Gemcitabine
BIOLOGICAL: Nab-paclitaxel
BIOLOGICAL: ALT-803

CA-ALT-803-01-15

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-09-23	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-01-24
First Submitted that Met QC Criteria 2015-09-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-01-27
First Posted (ACTUAL) 2015-09-24	Results First Posted N/A	Last Verified 2020-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase Ib/II ALT-803 w/ gemcitabine and nab-paclitaxel	BIOLOGICAL: Gemcitabine Intravenous Infusion; Patients will receive two 4-week treatment cycles consisting of gemcitabine given on Day 1, 8, 15, 29, 36, and 43. Eligible patients may receive up to 10 additional treatment cycles. BIOLOGICAL: Nab-paclitaxel Intravenous Infusion; Patients will receive two 4-week treatment cycles consisting of nab-paclitaxel given on Day 1, 8, 15, 29, 36, and 43. Eligible patients may receive up to 10 additional treatment cycles. BIOLOGICAL: ALT-803 Subcutaneous Injection; Patients will receive two 4-week cycles consisting of ALT-803 given on Day 2, 9, 16, 30, 37, and 44. Eligible patients may receive up to 10 additional treatment cycles.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Phase Ib/II ALT-803 w/ gemcitabine and nab-paclitaxel

BIOLOGICAL: Gemcitabine

Intravenous Infusion; Patients will receive two 4-week treatment cycles consisting of gemcitabine given on Day 1, 8, 15, 29, 36, and 43. Eligible patients may receive up to 10 additional treatment cycles.

BIOLOGICAL: Nab-paclitaxel

Intravenous Infusion; Patients will receive two 4-week treatment cycles consisting of nab-paclitaxel given on Day 1, 8, 15, 29, 36, and 43. Eligible patients may receive up to 10 additional treatment cycles.

BIOLOGICAL: ALT-803

Subcutaneous Injection; Patients will receive two 4-week cycles consisting of ALT-803 given on Day 2, 9, 16, 30, 37, and 44. Eligible patients may receive up to 10 additional treatment cycles.

Primary Outcome Measures	Measure Description	Time Frame
Determination of MTD; Phase Ib	Determine the maximum tolerated dose (MTD) level and designate the recommended dose level for phase II.	9 Months
Safety Profile (Number and severity of treatment related AEs); Phase Ib and II	Number and severity of treatment related adverse events (AEs) that occur or worsen after the first dose of study treatment	48 Months
Overall Survival; Phase II	Determine the 8.5 month overall survival of treated patients	8.5 Months

Secondary Outcome Measures	Measure Description	Time Frame
Objective response rate	Evaluate objective response rate in treated patients.	72 Months
Duration of response	Evaluate duration of response in treated patients.	72 Months
Time to progression	Evaluate time to progression in treated patients.	72 Months
Progression-free survival	Evaluate progression-free survival in treated patients.	72 Months
Biomarkers; Phase Ib	Measure the serum levels of the following including but not limited to Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Interferon-gamma (IFN-ɣ), Tumor necrosis factor-alpha (TNF-α) and Monocyte chemoattractant protein-1 (MCP-1)	36 Months
Determine the level of anti-ALT-803 antibodies in patient serum	Determine the level of anti-ALT-803 antibodies in patient serum	36 Months
Area under the plasma concentration-time curve from time zero to infinity (AUC); Phase Ib	Area under the plasma concentration-time curve from time zero to infinity (AUC)	36 Months
Correlation between the level of circulating cell free DNA in patient plasma and response to study treatment	Correlation between the level of circulating cell free DNA in patient plasma and response to study treatment	36 Months
Correlation between the level of tumor DNA in patient plasma and response to study treatment	Correlation between the level of tumor DNA in patient plasma and response to study treatment	36 Months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed diagnosis of pancreatic cancer.

For dose escalation phase (Phase Ib) distant metastatic disease or unresectable disease and not a candidate for down staging to resection.
For expansion phase (Phase II) distant metastatic disease only.
For dose escalation phase (Phase Ib) 0 or 1 prior lines of chemotherapy for advanced pancreatic cancer. Prior gemcitabine is allowed, however prior nab-paclitaxel is not allowed.
For expansion phase (Phase II) no prior therapy for pancreatic cancer is allowed except for adjuvant therapy as long as it was completed ≥ 6 months prior to study treatment start
Have at least one untreated and progressing tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumor
Prior radiation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment. Radiation therapy must have been completed at least 4 weeks prior to the baseline scan
Resolved acute effects of any prior therapy to baseline or Grade ≤1
The Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
Life expectancy ≥12 weeks
Glomerular Filtration Rate (GFR) > 40mL (milliliter)/min; Creatinine ≤ 1.5 x ULN (Upper limit of Normal)
Platelets ≥100,000/uL (microliter)
Hemoglobin ≥ 9g/dL
Absolute Lymphocytes ≥800/uL
Absolute neutrophil count/absolute granulocyte count ≥1500/uL
Total bilirubin ≤ 2.0 X ULN, or ≤ 3.0 X ULN (for patients with Gilbert's Syndrome)
aspartate aminotransferase, alanine aminotransferase ≤ 2.5 X ULN, or ≤ 5.0 X ULN (if liver metastasis present)
Normal clinical assessment of pulmonary function
Negative serum pregnancy test if female and of childbearing potential
Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations

No women who are pregnant or nursing
No known hypersensitivity to gemcitabine or nab-paclitaxel
No concurrent herbal or unconventional therapy
No prior therapy with IL-15 or IL-15 analog
No ongoing toxicity from prior anti-cancer treatment that may interfere with study treatment. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must resolve to grade 1 or baseline before administration of the study treatment.
No positive Hep C serology or active Hep B infection
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 New York Heart Association Class > II congestive heart failure
No marked baseline prolongation of QT/QTc interval
No known autoimmune disease requiring active treatment. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
No known prior organ allograft or allogeneic transplantation
No known HIV-positive or AIDS unless patient is on a stable highly active antiretroviral therapy (HAART) regimen, have CD4 (cluster of differentiation 4) counts >350, with no detectable viral load on quantitative polymerase chain reaction test
No untreated central nervous system metastases, or if treated must be neurologically stable for at least 2 weeks prior to enrollment
No corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
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
No active systemic infection requiring parenteral antibiotic therapy
No anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days before treatment start
No disease requiring systemic immunosuppressive therapy
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 3 years after surgical treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Hing C. Wong, Ph.D., Altor BioScience

Publications

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