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QUILT-3.052: NANT Non-Hodgkin Lymphoma (NHL) Vaccine: Combination Immunotherapy in Subjects With Relapsed CD20-positive NHL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03169790
Recruitment Status : Not yet recruiting
First Posted : May 30, 2017
Last Update Posted : October 30, 2017
Information provided by (Responsible Party):
NantKwest, Inc.

Brief Summary:
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with with CD20-positive NHL who have progressed on or after rituximab therapy.

Condition or disease Intervention/treatment Phase
Non Hodgkin Lymphoma Biological: avelumab Biological: bevacizumab Drug: capecitabine Drug: cyclophosphamide Drug: 5-Fluorouracil (5-FU) Drug: leucovorin Drug: nab-paclitaxel Drug: Lovaza Drug: Oxaliplatin Drug: rituximab Radiation: Stereotactic Body Radiation Therapy Biological: ALT-803 Biological: ETBX-061 Biological: haNK Phase 1 Phase 2

Detailed Description:
Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year or until they experience progressive disease (PD) or experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 67 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NANT Non-Hodgkin Lymphoma (NHL) Vaccine: Combination Immunotherapy in Subjects With Relapsed CD20-positive NHL
Estimated Study Start Date : December 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Nant NHL Vaccine
avelumab, bevacizumab, capecitabine, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, oxaliplatin, rituximab, stereotactic body radiation therapy, ALT-803,ETBX-061, and haNK.
Biological: avelumab
Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

Biological: bevacizumab
Recombinant human anti-VEGF IgG1 monoclonal antibody

Drug: capecitabine
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine

Drug: cyclophosphamide
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate

Drug: 5-Fluorouracil (5-FU)
5-fluoro-2,4 (1H,3H)-pyrimidinedione

Drug: leucovorin
Calcium N-[p-[[[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1)

Drug: nab-paclitaxel
5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine

Drug: Lovaza
Omega-3-acid ethyl esters

Drug: Oxaliplatin
cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)- O,O'] platinum

Drug: rituximab
Chimeric murine/human anti-CD20 monoclonal IgG1 kappa antibody

Radiation: Stereotactic Body Radiation Therapy

Biological: ALT-803
recombinant human super agonist interleukin-15 (IL-15) complex

Biological: ETBX-061
Ad5 [E1-, E2b-]-mucin 1[MUC1]

Biological: haNK
NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous [IV] Infusion

Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 [ Time Frame: 1 year ]
    Phase 1b primary endpoint (safety)

  2. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: 1 year ]
    Phase 2 primary endpoint (ORR by RECIST)

  3. ORR by Immune-related response criteria (irRC ) [ Time Frame: 1 year ]
    Phase 2 primary endpoint (ORR by irRC)

Secondary Outcome Measures :
  1. ORR by RECIST Version 1.1 [ Time Frame: 1 year ]
    Phase 1b secondary endpoint (ORR by RECIST)

  2. ORR by irRC [ Time Frame: 1 year ]
    Phase 1b secondary endpoint (ORR by irRC)

  3. Progression-free survival (PFS) by RECIST Version 1.1 [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PFS by RECIST)

  4. PFS by irRC [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PFS by irRC)

  5. Overall survival (OS): time from the date of first treatment to the date of death (any cause) [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (OS)

  6. Duration of response (DR): time from the date of first response (partial response (PR) or complete response (CR)) to the date of disease progression or death (any cause) whichever occurs first [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (DR)

  7. Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months [ Time Frame: 2 months ]
    Phase 1b and 2 secondary endpoint (DCR)

  8. Patient Reported Outcome (PRO) using the FLynnSI-18 questionnaire [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PROs)

  9. Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03 [ Time Frame: 1 year ]
    Phase 2 secondary endpoint (AEs)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
  3. Histologically confirmed relapsed CD20-positive NHL with progression on or within 6 months after rituximab therapy.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  5. Have at least 1 measurable lesion of ≥ 1.5 cm.
  6. Must have a recent tumor biopsy specimen obtained following the conclusion of the most recent anti-cancer treatment. If a historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
  7. Must be willing to provide blood samples, and, if considered safe by the Investigator, a tumor biopsy specimen at 8 weeks after the start of treatment.
  8. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  9. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment.

Exclusion Criteria:

  1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.
  2. Within 5 years prior to first dose of study treatment, any evidence of other active malignancies or brain metastasis except controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL).
  3. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
  4. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
  5. History of organ transplant requiring immunosuppression.
  6. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  7. Requires whole blood transfusion to meet eligibility criteria.
  8. Inadequate organ function, evidenced by the following laboratory results:

    1. White blood cell (WBC) count < 2,000 cells/mm3.
    2. Absolute neutrophil count < 1,500 cells/mm3.
    3. Platelet count < 100,000 cells/mm3.
    4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    6. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
    7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
    8. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).
  9. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
  10. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  11. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
  12. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
  13. Known hypersensitivity to any component of the study medication(s).
  14. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  15. Concurrent or prior use of a strong CYP3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.
  16. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
  17. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.
  18. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  19. Concurrent participation in any interventional clinical trial.
  20. Pregnant and nursing women.

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 identifier (NCT number): NCT03169790

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Contact: Jim Farmer 310-853-7522

Sponsors and Collaborators
NantKwest, Inc.

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Responsible Party: NantKwest, Inc. Identifier: NCT03169790     History of Changes
Other Study ID Numbers: QUILT-3.052
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: October 30, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Albumin-Bound Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors