A Study on Limiting Treatment Time With Acalabrutinib Combined With Obinutuzumab in People With CLL or SLL
A Study on Limiting Treatment Time With Acalabrutinib Combined With Obinutuzumab in People With CLL or SLL
This study will test the safety of limiting treatment time with acalabrutinib and
 obinutuzumab in people who have chronic lymphocytic leukemia (CLL) or small lymphocytic
 lymphoma (SLL). The researchers want to find out whether stopping the study drugs when the
 cancer responds to the treatment, followed by a period of observation in which no treatment
 is given, is better than, the same as, or worse than the usual approach. A usual treatment
 for CLL and SLL is to give the study drugs continuously until the cancer progresses, even if
 the disease is in remission. But when people receive these drugs for long periods of time,
 they can have serious side effects and their cancer can become resistant to treatment.
Inclusion Criteria:

 -  Signed informed consent form (ICF). Legally Authorized Representatives are permitted.

 -  Ability and willingness to comply with requirements of the study protocol

 -  ≥ 18 years-old

 -  Have documented previously untreated CLL or SLL per WHO criteria and require treatment
 per iwCLL guidelines

 -  ECOG performance status of 0, 1, or 2

 -  Participants must have adequate organ and marrow function as defined below:

 -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN), unless there is a
 disease involvement of the liver, hemolysis, or a known history of Gilbert's
 disease.

 -  Hemoglobin ≥ 8 g/dL without transfusion support, unless anemia is due to marrow
 involvement of CLL.

 -  Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L.

 -  AST and ALT ≤ 2.5 times the ULN.

 -  Creatinine clearance (CrCl) > 30 mL/min as calculated using modified Cockcroft-
 Gault or MDRD Formula

 -  PT/INR ≤ 2 times the ULN and aPTT ≤ 2 times the ULN unless the elevation in
 PT/INR or aPTT is solely attributable to direct oral anticoagulant.

 -  Platelet count without transfusion support must be ≥ 50,000 cells/mm3 or ≥ 30,000
 cells/mm^3 in subjects with documented bone marrow involvement, as determined locally.

 -  For women of childbearing potential: Agreement to remain abstinent (refrain from
 heterosexual intercourse) or use a highly effective contraceptive method (failure rate
 of < 1%) per year during the treatment period and for at least 18 months after the
 last dose of study medication. Women of childbearing potential must have a negative
 serum pregnancy test result within 3 days prior to initiation of study drug

 -  Women must refrain from donating eggs during this same period

 -  A woman is considered of childbearing potential if she is postmenarcheal, has not
 reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no
 identified cause other than menopause), and has not undergone surgical
 sterilization (removal of ovaries and/or uterus)

 -  Examples of contraceptive methods with a failure rate of < 1 % per year include
 bilateral tubal ligation, male sterilization, hormonal contraceptives that
 inhibit ovulation, hormone-releasing intrauterine devices, and copper
 intrauterine devices

 -  Examples of contraceptive methods with a failure rate of < 1 % per year include
 bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit
 ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices

 -  With female partners of childbearing potential, men must remain abstinent or use
 a condom plus an additional contraceptive method that together result in a
 failure rate of < 1% per year during the treatment period and for at least 6
 months after- the last dose of obinutuzumab; men must refrain from donating sperm
 during this same period

 -  With pregnant female partners, men must remain abstinent or use a condom during
 the treatment period and for at least 6 months after the last dose of
 obinutuzumab to avoid exposing the embryo

 -  The reliability of sexual abstinence should be evaluated in relation to the
 duration of the clinical trial and the preferred and usual lifestyle of the
 patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or
 post-ovulation methods) and withdrawal are not acceptable methods of
 contraception

 Exclusion Criteria:

 -  Prior CLL-directed therapy

 °Excluding corticosteroid therapy started for non-CLL related reasons or disease
 related symptom management (prednisone up to 20 mg daily). Topical or inhaled
 corticosteroids are permitted

 -  Transformation of CLL to aggressive lymphoma (Richter's transformation to NHL or
 Hodgkin's lymphoma, or pro-lymphocytic leukemia)

 -  CLL with deletion of chromosome 17p and/or TP53 mutation. Patients must have FISH or
 array CGH analysis and NGS for TP53 mutations locally as per SOC within 60 days of
 C1D1 (peripheral blood, bone marrow or lymph node with disease involvement are
 acceptable sources) as SOC.

 -  History of confirmed progressive multifocal leukoencephalopathy (PML)

 -  Known hypersensitivity to any active ingredient in the study drugs.

 -  Active bleeding, or presence of known bleeding disorder (e.g. von Willebrand's
 disease) or hemophilia.

 -  Any severe and/or uncontrolled medical conditions or other conditions that could
 affect their participation in the study such as:

 -  Clinically significant cardiac disease that includes symptomatic arrhythmia
 (subjects with controlled, asymptomatic atrial fibrillation or other atrial
 arrhythmias during screening are allowed to enroll on study)

 -  Intracranial hemorrhage, stroke within 6 months of study enrollment

 -  Symptomatic, or history of documented congestive heart failure (NY Heart
 Symptomatic, or history of documented congestive heart failure (NY Heart
 Association functional classification III-IV

 -  Myocardial infarction within 6 months of enrollment

 -  Concomitant use of medication known to cause QT prolongation or torsade's de
 pointes should be used with caution and at investigator's discretion

 -  Angina not well-controlled by medication

 -  Poorly controlled or clinically significant atherosclerotic vascular disease
 including cerebrovascular accident (CVA), transient ischemic attack (TIA),
 angioplasty, cardiac/vascular stenting within 6 months of study enrollment

 -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
 (excluding fungal infections of nail beds) at study enrollment, or any major episode
 of infection requiring treatment with IV antibiotics or hospitalization (relating to
 the completion of the course of antibiotics) within 2 weeks prior to cycle 1 day 1

 -  Requires the use of warfarin or equivalent Vitamin K antagonist

 -  Requires or received the following agents within 7 days prior to the first dose of
 acalabrutinib-obinutuzumab combination therapy:

 -  Patients who are positive for HCV antibody must be negative for HCV by polymerase
 chain reaction (PCR) to be eligible for study participation

 -  Patients with occult or prior HBV infection (defined as positive total hepatitis
 B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is
 undetectable by PCR. These patients must be willing to undergo sequential DNA
 testing as per institutional standards (every 1-3 months) and antiviral
 prophylaxis as per institutional standards.

 -  Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic
 purpura).

 -  Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before
 screening, this is subject to investigator's discretion

 -  Known infection with HIV (testing not required as part of screening)

 -  Receipt of live-virus vaccines within 28 days prior to the initiation of study
 treatment

 -  Pregnant or lactating, or intending to become pregnant during the study

 -  Major surgical procedures within 28 days of first dose of study drug. Note: if a
 subject had major surgery, they must have recovered adequately from any toxicity
 and/or complications from the intervention before the first dose of study drug.

 -  Malabsorption syndrome or other condition that precludes enteral route of
 administration; this is subject to investigator discretion

 -  Has difficulty with or is unable to swallow oral medication

 -  Concurrent participation in the treatment phase of an interventional clinical trial

 -  Unwilling or unable to participate in all required study evaluations and procedures.
 Unable to provide a signed and dated informed consent form (ICF) and authorization to
 use protected health information (in accordance with national and local patient
 privacy regulations).