Phase 1/2 Study Of Intratumoral G100 With Or Without Pembrolizumab or Rituximab In Patients With Follicular Non-Hodgkin’s Lymphoma

  • STATUS
    Recruiting
Updated on 22 December 2020
lymphomas
lymphoma
non-hodgkin's lymphoma

Summary

This is a multi-center Phase 1/2 open label trial of intratumoral G100 in patients with low grade NHL. Patients with NHL will be enrolled and receive G100 to an accessable tumor mass. Clinical response will be evaluated in the injected lesion and systemic (abscopal) responses will be evaluated in distal areas involved with tumor.

The study will be conducted in 5 parts.

  • In Part 1, Dose Escalation, 2 sequentially enrolled cohorts of patients will be treated at one of 2 dose levels of G100 using a standard escalation design. In this portion of the study, both follicular and marginal zone NHL will eligible.
  • In Part 2, 2 groups of patients with follicular NHL may be examined.  One group will be randomly assigned to receive either single agent G100 intratumorally at the maximum safe dose determined in Part 1 following local radiation or will receive the same treatment regimen sequentially administered with pembrolizumab. A second treatment group may be explored if the safety profile in Part 1 is acceptable. In this optional group, patients with injectable tumors of 4 cm or greater would be enrolled and treated with a higher dose of G100.
  • In Part 3, expansion of a higher dose (20µg of G100) in patients with follicular NHL will be enrolled to receive local radiation therapy and intratumoral G100 (no tumor size requirement in this arm).
  • In Part 4, Dose Escalation and Expansion, a dose of 20µg of G100 will be examined as a treatment of 1 or more tumor lesions (up to 4) with pembrolizumab in order to establish safety and examine clinical and biomarker responses in patients receiving increasing total systemic doses of G100.
  • In Part 5, Dose Escalation, increasing doses of G100 (in combination with rituximab) in a single tumor lesion will be examined. Once the highest dose has been established as safe, a Patient Expansion group may be treated.

The primary goal of this study is to determine the safety and tolerability of different doses of G100 when administered by intratumoral injection. The development of anti-tumor immune responses and preliminary evidence of clinical responses in local and distal tumor sites will also be examined.

 

Details
Condition Lymphoma, Non-Hodgkin's Lymphoma
Clinical Study IdentifierTX218233
Last Modified on22 December 2020

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Non-Hodgkin's Lymphoma or Lymphoma?
Follicular low-grade NHL (grades 1, 2, 3A)
In Parts 1-3, either treatment naive or relapsed or refractory following at least one prior treatment. For France, patients with either relapsed or refractory only. In Part 1 Dose Escalation only, in addition to follicular NHL, marginal zone B cell lymphomas: either treatment naive or relapsed or refractory following at least one prior treatment
In Part 4, enrollment is limited to relapsed or refractory follicular NHL patients who have received at least 3 prior systemic treatments, one of which was or included an anti-CD20 antibody
In Part 5, enrollment will include relapsed or refractory CD20+ follicular NHL following at least one but not more than 2 prior treatments
Tumor mass(es) accessible for intratumoral injection. Imaging assisted injections are allowed
For Parts 4 and 5, Measurable tumor mass(es) accessible for intratumoral injection must be present for treatment and assessment of response
≥18 years of age
Life expectancy of ≥6 months per the investigator
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
ECG without evidence of clinically significant arrhythmia or ischemia
If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use two methods of birth control or is considered highly unlikely to conceive during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment or if receiving rituximab, 12 months after last treatment
If male and sexually active with a FCBP, must agree to use effective contraception such as latex condom or is sterile (e.g., following a surgical procedure) during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment or if receiving rituximab, 12 months after last treatment
Exclusion Criteria
Cancer therapies, including chemotherapy, radiation (non-study regimen related), biologics or kinase inhibitors, granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) within 4 weeks prior to the first scheduled G100 dose
Investigational therapy within 4 weeks prior to G100 dosing
Prior administration of G100 or other intratumoral immunotherapeutics
Inadequate organ function including
Marrow: Peripheral blood leukocyte count (WBC) <3000/mm3, absolute neutrophil count ≤1500/mm3, platelets <75000/mm3, or hemoglobin <10 gm/dL
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) >2.5 × the upper limit of normal (ULN), total serum bilirubin >1.5 × ULN (patients with Gilbert's Disease may be included if their total bilirubin is 3.0 mg/dL)
Renal: Creatinine >1.5 × ULN
Other: international normalized ratio (INR) or partial thromboplastin time (PTT) >1.5 × ULN
Significant immunosuppression from
Concurrent, recent (≤4 weeks ago) or anticipated treatment with systemic corticosteroids at any dose, or
Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine or conditions such as common variable hypogamma¬globulinemia
Pregnant or nursing
Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
History of other cancer within 2 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ)
Recent (<1 week ago) clinically significant infection, active tuberculosis or evidence of active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease. In Parts 4 and 5, any involvement with lymphoma in a closed or confined space such as the retroorbital area will need to be pre-approved by the Medical Monitor
Significant autoimmune disease, including active non-infectious pneumonitis, with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy. (Replacement therapy for hypothyroidism or diabetes is allowed.)
Psychiatric, other medical illness or other condition that in the opinion of the PI prevents compliance with study procedures or ability to provide valid informed consent
History of significant adverse or allergic reaction to any component of G100, and if enrolled in Part 4, pembrolizumab and/or any of its excipients, and if enrolled in Part 5, anti-CD20 antibodies including rituximab and/or any of its excipients
Use of anti-coagulant agents or history a significant bleeding diathesis
Has received a live vaccine within 30 days prior to the first dose of study drug (Applies to patients who may receive either pembrolizumab or rituximab). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed
For patients enrolled in Part 4 with the potential to receive pembrolizumab
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis or interstitial lung disease
Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft versus host disease [GVHD].)
Has had an allogeneic tissue/solid organ transplant
Has received prior therapy with an anti-PD-1, anti-programmed death ligand (PD-L)1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials or was previously treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note