DNA Plasmid Encoding a Modified Human Telomerase Reverse Transcriptase (hTERT), Invac-1 in Chronic Lymphocytic Leukemia

NCT03265717 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: INVAC1-CT-201
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 2 study to assess the efficacy of INVAC-1, a DNA plasmid encoding a modified human telomerase reverse transcriptas (hTERT) protein, at a dose of 800 µg for 6 cycles 4 weeks apart on Minimal Residual Disease (MRD) eradication rate in the bone marrow, either as a single agent in a high risk "watch and wait" group (group 1 - 42 patients) or in combination with ibrutinib (group 2 - 42 patients), in patients with Chronic Lymphocytic Leukemia (CLL). Pharmacodynamics and safety will also be assessed.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Keywords

telomerase, tert, cancer vaccine

Outcome Measures

Primary Outcomes (1)

• Minimal Residual Disease (MRD) eradication rate in the bone marrow

  MRD eradication rate (by standardized 4-color flow cytometry, with a limit of detection of 0.01% CLL cells among total leucocytes in the bone marrow after 6 monthly injections of INVAC-1

  6 months

Secondary Outcomes (9)

• MRD eradication rate in blood after 6 monthly injections of INVAC-1

  6 months

• Duration of MRD eradication in bone marrow and blood

  approximately 3 years

• Cumulative incidence of partial and complete response by IWCLL 2018

  every 6 months for 3 years

• PFS as assessed by investigators according to IWCLL 2018 criteria

  approximately 3 years

• Time to next CLL treatment

  approximately 3 years

Study Arms (2)

Group 1: Untreated high risk "watch and wait"

EXPERIMENTAL

Newly diagnosed patients not eligible for any approved treatment (using NCI Working Group criteria), but having some poor prognosis characteristics (defined by MDACC nomogram criteria). Patients will be treated by INVAC-1 for 6 months and then MRD will be assessed. Patients will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who become MRD+ during follow-up, INVAC-1 can be resumed for one year.

Biological: INVAC-1

Group 2: Ibrutinib treated patients

EXPERIMENTAL

Patients who are receiving ibrutinib as 1st or 2nd line treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD. MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of the combined treatment period, MRD will be assessed. MRD-negative patients (defined as \<0.01% of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib. Then, they will be followed-up regularly for two years. Patients who become MRD-positive after being MRD-negative will resume ibrutinib single agent.

Biological: INVAC-1

Interventions

INVAC-1 BIOLOGICAL

Patients are treated by INVAC-1 for 6 cycles at 4-week intervals

Group 1: Untreated high risk "watch and wait"; Group 2: Ibrutinib treated patients

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• Rai stage 0 - II without active disease according to IWCLL 2018 criteria
• Predicted time to first treatment of ≤3 years according to MDACC nomogram.
• ECOG performance status of 0-2
• Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x ULN except Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used.
• Adequate renal function, defined as an estimated creatinine clearance ≥30 mL/min using the Cockcroft-Gault equation
• Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study
• Willingness of male and female patients, if sexually active, to use an effective barrier method of contraception during the study and for 3 months following the last dose of study drug
• Ability to provide written informed consent and to understand and comply with the requirements of the study

You may not qualify if:

• Any investigational agent(s) within 4 weeks prior to entry
• Uncontrolled autoimmune hemolytic anemia (Hgb \< 11g/deciliter) or idiopathic thrombocytopenic purpura (\< 100,000/µl)
• Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL
• Treatment with corticosteroids other than physiological replacement within the previous week or treatment with immunosuppressive medication within the previous week.
• Uncontrolled active systemic fungal, bacterial, viral, or other infection or requirement for intravenous (IV) antibiotics
• Known history of infection with human immunodeficiency virus (HIV)
• Serologic status reflecting active hepatitis B or C infection.
• History of stroke or intracranial hemorrhage within 6 months prior to enrolment
• Current life-threatening illness, medical condition, or organ-system dysfunction that could compromise patient safety or put the study at risk
• Breast-feeding or pregnant women, or patients for whom there is a risk of conception and who are unable or unwilling to use appropriate contraception (for male and female patients up to 4 months after end of ibrutinib.)
• Previous malignancy with life expectancy less than 6 months or requiring systemic treatment (except colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
• Known drug abuse/ alcohol abuse
• Severe organ failures or diseases, including: clinically relevant coronary disease, myocardial infarction or any other relevant cardiovascular disorder within 12 months before study entry, severe psychiatric illness and severe infection.
• Group 2: Ibrutinib treated patients
• Age ≥ 18 years old

Sponsors & Collaborators

• Invectys: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: August 29, 2017
• Study Start: July 25, 2018
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: July 8, 2020

Record last verified: 2020-07

Locations

US (1)