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Protocol Details

Phase 1 Trial of Human IL-15 (rhIL-15) and Obinutuzumab for Relapsed and Refractory Chronic Lymphocyte Leukemia

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

19-C-0024

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Clinical hold/Recruitment or enrollment suspended
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women and Fetuses;
Children

Special Instructions

Currently Not Provided

Keywords

Monoclonal Antibody Treatment;
Recombinant Human Interleukin-15;
Lymphoid Malignancy;
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

Recruitment Keyword(s)

None

Condition(s)

Leukemia;
Lymphocytic;
Chronic;
B-Cell

Investigational Drug(s)

Recombinant Human Interleukin-15

Investigational Device(s)

None

Intervention(s)

Drug: rhIL-15
Biological/Vaccine: obinutuzumab

Supporting Site

National Cancer Institute

Background:

Chronic lymphocytic leukemia (CLL) is a blood cancer. Recombinant human interleukin 15 (IL-15) is a manmade protein. Obinutuzumab is a protein made to deactivate cancer cells. Researchers want to see if treating people with CLL with both proteins improves their outcomes.

Objectives:

To find the safe dose of IL-15 with obinutuzumab. To identify its effects, including on the immune system and cancer.

Eligibility:

Adults at least 18 years old who have certain CLL that standard therapy has failed

Design:

Participants will be screened with:

-Medical history

-Physical exam

-Evaluation of ability to do daily activities

-Blood, heart, and urine tests

Participants may also be screened with:

-A small amount of bone marrow removed by needle in the hipbone

-Scans of the body and/or brain

The study will be done in 28-day cycles for up to 6 cycles.

Participants will get the study drugs through a catheter and pump.

Cycle 1: Participants will stay in the clinic for week 1. They will get:

-IL-15 as a continuous intravenous infusion over 24 hours on days 1-5

-Obinutuzumab as an infusion on 4 days, over about 4 hours. The doses for this will increase.

Other cycles: Participants will come to the clinic days 1 5 and get IL-15 as in cycle 1. They will get obinutuzumab on day 4.

During the study, participants:

-Will repeat screening tests

-Will get standard medicines for side effects

-May give blood, saliva, and tumor samples for research

After treatment, participants will have follow-up visits every 3 months for 1 year, then every 6 months for up to 5 years. After that, participants may be called or emailed.

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Eligibility

INCLUSION CRITERIA:

- Patients must have a confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma that expresses CD20 as confirmed by new/fresh peripheral blood sample collection and review by Laboratory of Pathology, NCI

- Measurable or evaluable disease

- Patients must have received prior treatment required as follows: CLL that is refractory or relapsed following therapy with a BTK inhibitor OR have relapsed/refractory CLL and are intolerant of BTK inhibitor therapy; in addition, patients with del(17p) must also be refractory or relapsed after, or intolerant to, therapy with venetoclax; patients who have received prior obinutuzumab are eligible regardless of response to the drug.

- Active disease requiring treatment, as defined by at least one of the following (per IWCLL 2018 consensus criteria):

-- Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (Hb <10 g/dL) and/or thrombocytopenia (platelet counts <100 (SqrRoot) 10^9/L).

-- Massive (i.e., greater than or equal to 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.

-- Massive nodes (i.e., greater than or equal to 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.

-- Progressive lymphocytosis with an increase of greater than or equal to 50% over a 2-month period, or lymphocyte doubling time (LDT) <6 months.

-- Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids.

-- Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine).

-- Disease-related symptoms as defined by any of the following:

--- Unintentional weight loss greater than or equal to 10% within the previous 6 months.

--- Significant fatigue (ie, ECOG performance scale 2 or worse; cannot work or unable to perform usual activities).

--- Fevers 38.0 degree C for 2 or more weeks without evidence of infection.

--- Night sweats for greater than or equal to 1 month without evidence of infection.

- greater than or equal to 18 years of age on day of signing informed consent

NOTE: Because no dosing or adverse event data are currently available on the use of rhIL-15 in combination with obinutuzumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

- ECOG performance status less than or equal to 1 (Karnofsky greater than or equal to 80%; or less than or equal to 2 (Karnofsky >60%) if the decrease in the performance status is CLL-related and

constitutes a criterion for active treatment

- Adequate organ function as evidenced by the following laboratory parameters:

-- Absolute neutrophil count (ANC) greater than or equal to 750 /mcL

-- Platelets greater than or equal to 50,000 / mcL (transfusions not permitted)

-- Hemoglobin greater than or equal to 9 g/dL (transfusions permitted)

-- Serum creatinine less than or equal to 1.5 X upper limit of normal (ULN)

-- Serum total bilirubin less than or equal to 1.5 X ULN OR Direct bilirubin less than or equal to ULN for patients with total bilirubin levels > 1.5 ULN

-- AST (SGOT) and ALT (SGPT) less than or equal to 3 X ULN

- Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment, and for at least 18 months after the last dose of obinutuzumab. The effects of rhIL-15 and obinutuzumab on the developing human fetus are unknown. Additionally, CD20-depleting agents are known to produce opportunistic infections, causing fetal B-cell depletion in animal studies, and may be teratogenic. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. WOCBP must have a negative pregnancy test (HCG blood or urine) during screening.

- Ability of patient to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

- Current or prior anti-cancer treatment prior to the first dose of rhIL-15 as defined below:

-- Chemotherapy, targeted small molecule therapy, or other anti-cancer treatment not otherwise specified below within 2 weeks

-- Radiation therapy within 2 weeks

-- Anti-cancer monoclonal antibody (mAb) treatment within 4 weeks

-- Use of an investigational agent (e.g., biologic, drug, or other) within 4 weeks

-- Allogeneic stem cell transplant within 100 days

-- Systemic treatment for graft versus host disease (GVHD), including but not limited to oral or parenteral corticosteroids, ibrutinib, and extracorporeal phototherapy, within the last 12 weeks

- Persisting toxicity related to prior therapy (including GVHD) of grade > 1, with the exception of the following: alopecia or sensory neuropathy grade less than or equal to 2, or other grade less than or equal to 2 not constituting a safety risk based on investigator's judgment

- Current use of immunosuppressive medication, EXCEPT for the following:

-- Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);

-- Systemic corticosteroids at physiologic doses less than or equal to 10 mg/day of prednisone or equivalent; or,

-- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

- Presence of Richter s transformation.

- Patients requiring immediate cytoreduction, if they had no prior treatment with a drug that has an established clinical benefit.

- Presence of uncontrolled intercurrent illnesses including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cognitive impairment, active substance abuse, or psychiatric illness/social situations that in the view of the Investigator would preclude safe treatment and limit compliance with study requirements

- Presence of active bacterial infections, documented HIV infection, PCR evidence for active or chronic hepatitis B or hepatitis C, or positive screening HBV/HCV serology without documentation of successful curative treatment

- Asthma requiring chronic inhaled or oral corticosteroids, or history of asthma requiring mechanical ventilation; patients with a history of mild asthma that are on or can be switched to non-corticosteroid bronchodilator regimens are eligible

- Active or history of any autoimmune disease thought to be unrelated to their CLL

- Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding. Because there is no significant preclinical information regarding the risks to a fetus or a newborn infant, all pregnant or breastfeeding woman will be excluded from participation in this trial

- Received a live vaccine within 30 days of planned start of study therapy. NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist ) are live attenuated vaccines, and are not allowed

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to rhIL-15 or obinutuzumab, unless felt to be in the best interests of the patient in the opinion of the investigator

- Known additional malignancy that requires active systemic treatment


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Milos Miljkovic, M.D.
National Cancer Institute (NCI)



NCI Medical Oncology Referral Office
National Cancer Institute (NCI)

(240) 760-6050
ncimo_referrals@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT03759184

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