ot applicable
- Conditions
- Chronic Lymphocytic LeukemiaMedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2015-005758-36-IT
- Lead Sponsor
- TG THERAPEUTICS, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 450
1. B-cell CLL (treatment naïve or previously treated) that warrants treatment consistent with accepted IWCLL criteria (Hallek 2008) for
initiation of therapy. Any of the following conditions constitute CLL that warrants treatment:
a. Evidence of progressive marrow failure as manifested by the onset or
worsening of anemia and/or thrombocytopenia, or
b. Massive (i.e., lower edge of spleen = 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or
c. Massive (i.e., = 10 cm in the longest diameter), progressive, or
symptomatic lymphadenopathy, or
d. Progressive lymphocytosis in the absence of infection, with an
increase in blood absolute lymphocyte count (ALC) >50% over a 2-month period or lymphocyte doubling time of <6 months (as long as initial ALC was =30,000/uL), or
e. Autoimmune anemia and/or thrombocytopenia that is poorly
responsive to corticosteroids or other standard therapy, or
f. Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs occurring in the absence of
evidence of infection:
i. Unintentional weight loss of =10% within the previous 6
months, or
ii. Significant fatigue (= Grade 2), or
iii. Fevers >100.5°F or 38.0°C for =2 weeks, or
iv. Night sweats for >1 month.
2. Adequate organ system function, defined as follows:
a. Absolute neutrophil count (ANC) > 1,000 /mm^3 (uL) platelet count > 50,000mm^3 (uL).
b. Total bilirubin =1.5 times the upper limit of normal (ULN)
c. Alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) =2.5 x ULN if no liver involvement or =5 x the ULN if known liver involvement
d. Calculated creatinine clearance >30 mL/min (as calculated by the Cockcroft-Gault formula)
3. Presence of measurable lymphadenopathy, defined as the presence of > 1 nodal lesion that measures > 2.0 cm in the longest diameter (LD) and > 1.0
cm in the longest perpendicular diameter (LPD) as assessed by computed tomography (CT) or magnetic resonance imaging (MRI)
4. ECOG performance status = 2
5. Male or female = 18 years of age
6. Ability to swallow and retain oral medication
7. Female patients who are not of child-bearing potential (see Appendix B-
Contraceptive Guidelines and Pregnancy), and female patients of childbearing potential who have a negative serum pregnancy test within 3 days prior to Cycle 1, Day 1. Female patients of child-bearing potential, and male partners must consent to use a medically acceptable method of
contraception throughout the study period and for 4 months after the last dose of ublituximab or TGR-1202, or 18 months after the last dose of obinutuzumab, or at least 4 weeks after the last dose of chlorambucil.
8. Willingness and ability to comply with trial and follow-up procedures, and give written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 225
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 225
1. Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor
embolization) or any investigational drug within 21 days of randomization (contact sponsor for < 21 day washout period requests)
a. Corticosteroid therapy started at least 7 days prior to study entry
(prednisone =10 mg daily or equivalent) is allowed as clinically
warranted. Topical or inhaled corticosteroids are permitted.
2. Autologous hematologic stem cell transplant within 3 months of study entry. Prior Allogeneic hematologic stem cell transplant is excluded.
3. Evidence of chronic active Hepatitis B (HBV, not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody) or chronic active Hepatitis C infection (HCV), cytomegalovirus (CMV), or
known history of HIV. If HBc antibody, HCV antibody or CMV is positive the subject must be evaluated for the presence of HBV, HCV, or CMV by DNA (PCR) - See Appendix D.
4. Known histological transformation from CLL to an aggressive lymphoma (i.e. Richter’s transformation)
5. Prior exposure to idelalisib (CAL-101), duvelisib (IPI-145), ACP-319, or any drug that specifically inhibits phosphoinositide-3-kinase (PI3K)
6. Patients who have received prior therapy with obinutuzumab. Patients who are refractory to prior chlorambucil (defined as disease progression
while receiving or within 6 months of completion of a chlorambucil based regimen).
7. Evidence of ongoing systemic bacterial, fungal or viral infection, except
localized fungal infections of skin or nails. NOTE: Patients may be
receiving prophylactic antiviral or antibacterial therapies at investigator discretion. Use of anti-pneumocystis and antiviral prophylaxis is required for patients on TGR-1202 arms.
8. Live virus vaccines prior to or during obinutuzumab or ublituximab
therapy.
9. History of anaphylaxis (excluding infusion related reactions) in association with previous anti-CD20 administration
10. Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
a. Symptomatic, or history of documented congestive heart failure (NY
Heart Association functional classification III-IV [see Appendix C – NYHA Classifications])
b. Myocardial infarction within 6 months of randomization
c. QTcF >470 msec
d. Angina not well-controlled by medication
e. Poorly controlled or clinically significant atherosclerotic vascular
disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within 6 months of randomization.
11. Malignancy within 3 years of study enrollment except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer,
carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localized prostate
cancer and PSA <1.0 mg/dL on 2 consecutive measurements at least 3 months apart with the most recent one being within 4 weeks of study
entry.
12. Women who are pregnant or lactating.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method