NM-IL-12 in Cutaneous T-Cell Lymphoma (CTCL) Undergoing Total Skin Electron Beam Therapy (TSEBT)

NCT02542124 | Unknown Phase 2

• 2 other identifiers: NM-ONC-0011R44CA192576-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

In the proposed study, NM-IL-12 will be evaluated as immunotherapy to increase antitumor efficacy against CTCL, while reducing skin-related toxicity, when combined with low-dose TSEBT therapy. Determination of the maximum tolerated dose (MTD) for NM-IL-12 is not planned in this study, rather, a pre-defined starting dose will be explored; this dose is based on two safety and tolerability studies of NM-IL-12 in healthy volunteers.

Conditions

Cutaneous T Cell Lymphoma (CTCL); Mycosis Fungoides; Sézary Syndrome

Keywords

CTCL; Total Skin Electron Beam Therapy (TSEBT); Mycosis fungoides; Sézary syndrome; recombinant human Interleukin-12 (rHuIL-12); T Cell

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability will be evaluated on the basis of the following parameters (Vital signs, physical examination,Toxicity according to the NCI CTCAE, Immunogenicity evaluated by the presence of anti-drug antibody) :

  General safety: Vital signs (temperature, blood pressure, pulse rate, respiratory rate) and physical examination. Toxicity according to the NCI CTCAE (v4.03) for AEs and clinical laboratory profile; AEs will be collected in all patients who received at least one dose of NM-IL-12 and up to four weeks post last NM-IL-12 dose. Immunogenicity of NM-IL-12 will be evaluated by the presence of anti-drug antibody (ADA)

  107 weeks

Secondary Outcomes (2)

• Clinical Response measured by a modified severity-weighted assessment tool (mSWAT)

  107 weeks

• Progression free survival

  107 weeks

Study Arms (1)

NM-IL-12 and TSEBT

EXPERIMENTAL

TSEBT and subcutaneous doses of NM-IL-12

Biological: NM-IL-12 and TSEBT

Interventions

NM-IL-12 and TSEBT BIOLOGICAL

The LD-TSEBT treatment will start on Day 1 of the study. NM-IL-12 will be administered subcutaneously.

Also known as: HemaMax, rHu-IL12, LD-TSEBT

NM-IL-12 and TSEBT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Biopsy-confirmed CD4+ mycosis fungoides or Sézary syndrome, stage IB to IIIB
• The patient is eligible for TSEBT
• Eastern Cooperative Oncology Group (ECOG) of ≤ 2.
• Adequate bone marrow function: WBC \> 2000/μL; platelet count \> 75,000/μL; Neutrophil count \> 1000/μL, without use of colony stimulating factors (CSF).
• Required washout period for prior therapies Topical therapy: 2 weeks
• Phototherapy (PUVA): 4 weeks
• Local Skin Radiation Therapy (\< 10% skin surface): 4 weeks
• Retinoids: 4 weeks
• Interferons: 4 weeks
• Low dose methotrexate: 4 weeks
• HDAC inhibitors: 8 weeks
• Women of child-bearing potential must have negative serum pregnancy test and use accepted highly effective methods of birth control throughout the study and for 90 days after dosing and must agree to use effective contraception.
• Male patients must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception during the study and for 90 days after dosing.
• Adequate hepatic function: bilirubin ≤1.5 x upper limit of normal (ULN), AST ≤2.5 x ULN, ALT ≤2.5 x ULN, alkaline phosphatase (liver fraction) ≤2.5 x ULN

You may not qualify if:

• Biopsy confirmed CD8+ CTCL histology
• Large cell transformation
• Prior systemic use of any immunosuppressive chemotherapy (except low dose methotrexate) and/or monoclonal antibody treatment for CTCL
• Prior courses of TSEBT (Note: localized skin-directed radiotherapy is allowed if administered at least 4 weeks prior to initiation on study).
• Concomitant use of any anti-cancer therapy or immune modifier.
• Prior allogeneic hematopoietic cell transplant.
• Any ongoing infection whether receiving or not receiving antibiotics or have received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.
• Known history of human immunodeficiency virus (HIV), hepatitis B or C
• For women on estrogen based contraceptives, family history of venous thromboembolism (VTE) and/or risk factors predisposing for VTE and other medical conditions known to be associated with VTE.
• History of prior malignancy with the exception of cervical intraepithelial neoplasia, non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA \<1.0). Patients with a history of other malignancies must have undergone potentially curative therapy and have no evidence of that disease for five years
• Uncontrolled intercurrent illness, condition, or circumstances that could limit compliance with the study, including, but not limited to the following: acute or chronic graft versus host disease, uncontrolled diabetes mellitus or hypertension, or psychiatric conditions
• Any other medical issue, including laboratory abnormalities, deemed by the Investigator to be likely to interfere with patient participation
• Unresolved toxicity from previous anticancer therapy or incomplete recovery from surgery
• Major surgery within 12 weeks of enrolment
• Medically significant cardiac event or unstable cardiovascular function defined as:

Sponsors & Collaborators

• Neumedicines Inc.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (5)

• Gokhale MS, Vainstein V, Tom J, Thomas S, Lawrence CE, Gluzman-Poltorak Z, Siebers N, Basile LA. Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects. Exp Hematol Oncol. 2014 Apr 11;3(1):11. doi: 10.1186/2162-3619-3-11.

  PMID: 24725395 BACKGROUND

• Gluzman-Poltorak Z, Vainstein V, Basile LA. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: evidence for the development of a frontline radiation medical countermeasure. Am J Hematol. 2014 Sep;89(9):868-73. doi: 10.1002/ajh.23770. Epub 2014 Jun 19.

  PMID: 24852354 BACKGROUND

• Gluzman-Poltorak Z, Mendonca SR, Vainstein V, Kha H, Basile LA. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation. J Hematol Oncol. 2014 Apr 6;7:31. doi: 10.1186/1756-8722-7-31.

  PMID: 24708888 BACKGROUND

• Basile LA, Ellefson D, Gluzman-Poltorak Z, Junes-Gill K, Mar V, Mendonca S, Miller JD, Tom J, Trinh A, Gallaher TK. HemaMax, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates. PLoS One. 2012;7(2):e30434. doi: 10.1371/journal.pone.0030434. Epub 2012 Feb 24.

  PMID: 22383962 BACKGROUND

• Rook AH, Wood GS, Yoo EK, Elenitsas R, Kao DM, Sherman ML, Witmer WK, Rockwell KA, Shane RB, Lessin SR, Vonderheid EC. Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses. Blood. 1999 Aug 1;94(3):902-8.

  PMID: 10419880 BACKGROUND

Related Links

• Single Low-dose rHuIL-12 Safely Triggers Multilineage Hematopoietic and Immune-mediated Effects.

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

Interleukin-12 Subunit p35

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukin-12; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Youn H Kim, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 4, 2015
• Study Start: December 1, 2015
• Primary Completion: February 1, 2019
• Study Completion: May 1, 2019
• Last Updated: November 16, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)