Trial Title:
Phase 2 Trial of Obinutuzumab and CC-99282 for Patients With Previously Untreated High Tumor Burden Follicular Lymphoma
NCT ID:
NCT06108232
Condition:
Follicular Lymphoma
Tumor
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Obinutuzumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
Given by IV (vein)
Arm group label:
Obinutuzumab+CC-99282
Other name:
GA101
Other name:
Gazyva
Other name:
RO5072759
Intervention type:
Drug
Intervention name:
CC-99282
Description:
Given by PO
Arm group label:
Obinutuzumab+CC-99282
Summary:
To learn if obinutuzumab in combination with CC-99282 can help to control previously
untreated, high tumor burden FL
Detailed description:
Objectives:
Primary Objectives:
• To determine the efficacy of obinutuzumab in combination with CC-99282 as determined by
complete response (CR) rate after six cycles of combination treatment for patients with
previously untreated, high tumor burden follicular lymphoma (FL).
Secondary Objectives:
• To determine best overall response rate (ORR), duration of response (DOR), time to next
treatment, CR rate at 30 months (CR30), progression-free survival (PFS), overall survival
(OS), and evaluation of safety of obinutuzumab and CC-99282 as treatment for previously
untreated patients with FL.
Exploratory Objective:
- To determine the biomarkers that correlates with response and mechanisms of
resistance to obinutuzumab and CC-99282 in FL.
- To determine the quality of life in patients with FL receiving obinutuzumab and
CC-99282
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients must meet the following criteria for study entry:
- Histologically diagnosed follicular lymphoma grade 1-3a
- Have no prior systemic treatment for lymphoma
- Stage II, III or IV disease
- Age ≥18 years
- Performance status ≤2 on the ECOG scale
- High-tumor burden disease based on GELF criteria36
- A nodal or extranodal (except spleen) mass > 7 cm in its greater diameter
- At least 3 nodal or extranodal sites ≥ 3 cm in diameter
- Presence of at least one B symptom
- Fever (>38 ℃), night sweats, weight loss > 10% in the past 6 months
- Symptomatic splenomegaly (or size >13cm)
- Impending organ compression or involvement (ureteral, orbital, gastrointestinal)
- Any of the following cytopenias due to bone marrow involvement of lymphoma
- Hemoglobin ≤ 10 g/dL
- Platelets ≤ 100 x 109/L
- Absolute neutrophil count (ANC) < 1.5x109/L
- Pleural effusion or ascites
- Bi-dimensionally measurable disease, with at least one nodal lesion ≥ 1.5 cm or one
extra-nodal lesion > 1 cm in longest diameter by CT, PET/CT, and/or MRI
- Bulky disease is defined as > 10 cm in its greater diameter
- Patients must have adequate organ and marrow function as defined below:
- Total bilirubin ≤ 1.5 ULN, unless consistent with Gilbert's (ratio between total and
direct bilirubin > 5)
- AST and ALT ≤ 3x upper limit of normal (ULN)
- Alkaline phosphatase < 2.5 ULN
- Creatinine clearance >50 ml/min calculated by modified Cockcroft-Gault formula
- Blood counts below if without bone marrow lymphoma involvement
- Hemoglobin ≥ 8 g/dL
- Platelets ≥ 75 x 109/L
- Absolute neutrophil count (ANC) ≥ 1.5x109/L
All subjects must:
- Have an understanding that the study drug could have a potential teratogenic risk.
- Agree to refrain from donating blood while on study treatment, during dose
interruptions and for at least 28 days following the last dose of study treatment.
- Agree not to share study medication with another person.
- Agree to follow all requirements defined in the Pregnancy Prevention Program (see
Appendix 14.1) for CC-99282 Pregnancy Prevention Plan for Subjects in Clinical
trials.
- Females must agree to abstain from breastfeeding while taking CC-99282 and for at
least 6 months and 2 weeks after the last dose of CC-99282
- Females of childbearing potential (FCBP§) must:
- Have two negative pregnancy tests as verified by the investigator prior to starting
study therapy. She must agree to ongoing pregnancy testing during the course of the
study, and after end of study therapy. This applies even if the subject practices
true abstinence* from heterosexual contact.
- Either commit to true abstinence* from heterosexual contact (which must be reviewed
on a monthly basis and source documented) or agree to use, and be able to comply
with two forms of contraception: one highly effective, and one additional effective
(barrier) measure of contraception without interruption 28 days prior to starting
IP, during the study treatment (including dose interruptions), and for 6 months and
2 weeks for women and 3 months and 2 weeks for men after the last dose of CC-99282
and for 12 months after the last dose of obinutuzumab, whichever is longer.
Contraception requirements are detailed in Appendix 14.1.
- Male subjects must:
- Practice true abstinence* (which must be reviewed on a monthly basis and source
documented) or agree to use a condom (Appendix 14.1) during sexual contact with a
pregnant female or a female of childbearing potential while participating in the
study, during dose interruptions and for at least 3 months and 2 weeks after the
last dose of CC-99282 or obinutuzumab, whichever is longer, even if he has undergone
a successful vasectomy.
- Must agree to refrain from donating sperm while on study treatment, during dose
interruptions, and for at least 3 months and 2 weeks after the last dose of CC-99282
or obinutuzumab, whichever is longer.
- Sign an informed consent document indicating that they understand the purpose of and
procedures required for the study, including biomarkers, and are willing to
participate in the study.
The investigator is responsible for: ensuring that the patient understands the potential
risks and benefits of participating in the study; ensuring that informed consent is given
by each patient, this includes obtaining the appropriate signatures and dates on the
informed consent document prior to the performance of any study procedures and prior to
the administration of study treatment; answering any questions the patient may have
throughout the study and sharing in a timely manner any new information that may be
relevant to the patient's willingness to continue his or her participant in the trial.
Subjects will undergo a brief physical exam including a brief exam to determine cognitive
review. No one without capacity to personally consent will be enrolled. Patients have
medical decision-making capacity if they can demonstrate understanding of the situation,
appreciation of the consequences of their decision, and reasoning in their thought
process, and if they can communicate their wishes.
A determination of lack of decision-making capacity shall be made after an appropriate
medical evaluation that concludes there is little or no likelihood that the participant
will regain decision-making capacity in a reasonable period of time.
§A FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a
hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal
(amenorrhea following cancer therapy does not rule out childbearing potential) for at
least 24 consecutive months (ie, has had menses at any time in the preceding 24
consecutive months).
*True abstinence is acceptable when this is in line with the preferred and usual
lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria:
Subjects will be ineligible for this study if they meet any of following criteria:
- Known active central nervous system lymphoma or leptomeningeal disease
- Any prior history of other malignancy besides B-NHL, unless the patient has been
free of disease for ≥ 3 years and felt to be at low risk for recurrence by the
treating physician, except:
- Adequately treated localized skin cancer without evidence of disease.
- Adequately treated cervical carcinoma in situ without evidence of disease.
- Any life-threatening illness, medical condition, or organ system dysfunction which,
in the investigator's opinion, could compromise the subject's safety, interfere with
the absorption or metabolism of lenalidomide capsules, or put the study outcomes at
undue risk
- Uncontrolled human immunodeficiency virus (HIV), or active Hepatitis C Virus, or
active Hepatitis B Virus infection, or any uncontrolled active significant
infection, including suspected or confirmed JC virus infection and SARS-CoV2
- Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation
prophylaxis unless contraindicated. Hepatitis B or C serologic status: subjects who
are hepatitis B core antibody (anti-HBc) positive and who are surface antigen
negative will need to have a negative polymerase chain reaction (PCR). Those who are
hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be
excluded. Subjects who are hepatitis C antibody positive will need to have a
negative PCR result. Those who are hepatitis C PCR positive will be excluded.
Subjects with a history of Hepatitis C who received antiviral treatment are eligible
as long as PCR is negative.
- History of immunodeficiency (with the exception of hypogammaglobulinemia) or
concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc.,
or chronic administration glucocorticoid equivalent of >10mg/day of prednisone)
within 28 days of the first dose of study drug
- Requires chronic treatment with strong CYP3A inhibitors (List in Table 1). Patients
can be eligible after discontinuation of the perpetrator and a sufficient washout
period of 7-days or 5 half-lives, whichever is longer.
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined
by the New York Heart Association Functional Classification. Subjects with
controlled, asymptomatic atrial fibrillation during screening can enroll on study
- Significant screening electrocardiogram (ECG) abnormalities including left bundle
branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd
degree block.
- QTcF ≥ 470 msec
- Active bleeding or known bleeding diathesis (e.g., von Willebrand's disease) or
hemophilia
- History of stroke or intracranial hemorrhage within 6 months prior to study entry.
- Vaccinated with live, attenuated vaccines within 4 weeks of study entry.
- Lactating or pregnant subjects
- Administration of any investigational agent within 28 days of first dose of study
drug.
- Patients who have undergone major surgery within 28 days or minor surgery within 3
days of first dose of study drug.
- Patients taking corticosteroids during the last 4 weeks, unless administered at a
dose equivalent to < 10 mg/day prednisone (over these 4 weeks).
- Life expectancy < 6 months
- Neuropathy > Grade 1
- Prior exposure to CD20 mAb or IMiDs, independently from indication
- Patients who have difficulty with or are unable to swallow oral medication, or have
disease significantly affecting gastrointestinal function that would limit
absorption of oral medication
- Patients who have an active autoimmune disease that has required systemic treatment
in past 2 years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
- Patients who have a history of (non-infectious) pneumonitis that required steroids
or has current pneumonitis.
- Known history of symptomatic deep vein thrombosis or pulmonary embolism
- Known history of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
or drug rash with eosinophilia and systemic symptoms (DRESS)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dai Chihara, M D, PhD
Phone:
713-792-2860
Email:
dchihara@mdanderson.org
Investigator:
Last name:
Dai Chihara, M D, PhD
Email:
Principal Investigator
Start date:
March 15, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06108232
http://www.mdanderson.org
