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Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Alemtuzumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Antimetabolites

CFAR: Cyclophosphamide 250 mg/m\^2/day intravenous (IV) Days 3-5, Fludarabine 25 mg/m\^2/day IV Days 3-5, Alemtuzumab 30 mg IV Days 1, 3 and 5 over 2-4 hours, repeated every four weeks for a total of 6 planned cycles, and Rituximab Cycle 1 (Week 1): 375 mg/m\^2/day IV Day 2 over 4- 6 hours, Cycle 2 - 6 (Week 1): 500 mg/m\^2/day IV Day 2 over 4- 6 hours.

25 mg/m\^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles.

250 mg/m\^2/day IV on Days 3-5; repeated every four weeks for a total of 6 planned cycles.

30 mg IV on Days 1, 3 and 5 over 2-4 hours; repeated every four weeks for a total of 6 planned cycles.

Cycle 1 (Week 1): 375 mg/m\^2/day IV on Day 2 over 4- 6 hours

Cycle 2 - 6 (Week 1): 500 mg/m\^2/day IV on Day 2 over 4- 6 hours

William G. Wierda, MD, PhD, BS

The goal of this clinical research study is to learn if the combination of fludarabine, cyclophosphamide, alemtuzumab, and rituximab is effective in treating chronic lymphocytic leukemia in patients who have already been treated with chemotherapy.

Primary Objectives:

Evaluate the therapeutic efficacy, including the complete remission (CR), nodular partial remission (NPR), and partial remission (PR) rates (overall response) of combined cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR) in previously treated patients with Chronic Lymphocytic Leukemia (CLL).

Second Objectives:

* Assess the toxicity profile of CFAR in previously treated patients with CLL.
* Monitor for infection and determine incidence and etiology of infection including cytomegalovirus in patients treated with CFAR.
* Evaluate molecular remission by polymerase chain reaction (PCR) for the clonal immunoglobulin heavy chain variable gene in responding patients treated with CFAR.
* Assess immune parameters, including pretreatment, during treatment, and post-treatment blood T-cell counts and subset distribution and serum immunoglobulin levels in patients treated with CFAR.

Fludarabine is a chemotherapy drug that is approved for the treatment of CLL. Cyclophosphamide is also a chemotherapy drug that is commonly used in the treatment of CLL. Rituximab and alemtuzumab are special proteins that specifically target and attach to proteins on leukemia cells. These targeted proteins may also be present on normal blood cells. When these drugs bind to the proteins on leukemia cells, they may help to stop or slow the growth of the disease. The combination of fludarabine, cyclophosphamide and rituximab has been used in the treatment of CLL. The purpose of this study is to determine if there is added benefit with the addition of alemtuzumab to this combination.

Before treatment starts, you will have a complete physical exam, including blood tests (about 3 tablespoons). You may have either a chest x-ray or a computed tomography (CT) scan if your doctor feel this is necessary. If you have not had a bone marrow sample collected in the past 4 months, you will have a bone marrow sample collected at this time. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood pregnancy test.

During the study, you will have up to 6 "cycles" of treatment. A cycle is made up of treatment with the study drugs for 5 days in a row, then around 31/2 weeks (23 days) of no treatment with the study drugs. On Days 1, 3, and 5 of each cycle you will receive alemtuzumab through a needle in a vein. On Day 2 of each cycle you will receive rituximab through a needle in a vein. Cyclophosphamide and fludarabine will be given separately on Days 3, 4, and 5 of each cycle through a needle in a vein. In addition to the study drugs, you may also be given fluids by vein. The combination treatment will be repeated every 4 weeks (one cycle) for a total of up to 6 cycles. This treatment will be given on an outpatient basis. The injections for each daily treatment visit should take less than 6 hours.

You will receive acetaminophen (Tylenol) by mouth and diphenhydramine hydrochloride (Benadryl) by mouth or vein 30 - 60 minutes before each dose of rituximab and alemtuzumab. You will also receive hydrocortisone (a steroid) by vein before each dose of alemtuzumab. These drugs will be used to help decrease side effects. If side effects occur during a treatment, the doses of the drugs may be adjusted (up or down) until the symptoms are gone. Also, if you experience side effects during treatment, you must stay in the clinic for 2 hours after the drug is given to be observed.

If you begin to experience side effects due to treatment, the dose(s) of the drug(s) may be lowered or the treatment may be temporarily stopped until the symptoms are gone.

During the treatment and for two months after completion of treatment you will need to take prophylactic antibiotics to prevent you from developing infection. Trimethoprim/sulfamethoxazole (Bactrim DS) is a sulfa-drug and you will be given this to prevent a type of pneumonia called PCP pneumonia. If you are allergic to sulfa drugs, an equivalent antibiotic will be given. You will take Valtrex to prevent virus reactivation including herpes. If you are allergic to Valtrex, an equivalent antibiotic will be given. You may receive an additional antibiotic to suppress another virus, cytomegalovirus called Valcyte. You may also take allopurinol for the first week of the first course of treatment. This will help prevent kidney damage from rapid destruction of your leukemia cells.

During the first cycle of treatment, you will have blood drawn (about 2 tablespoons) for blood tests once a week. Then, these blood tests will be repeated before the start of each additional cycle (every 4 weeks).

After 3 cycles of treatment, you will have a physical exam and blood tests (about 2 tablespoons). You may also have either an x-ray or a CT scan. You will have another bone marrow sample collected. These tests will be used to see if the disease is responding to treatment. If it is found that the disease is not responding to treatment after the first 3 cycles of therapy, you will be taken off the study and your doctor will discuss other treatment options with you. If it is found that the disease is responding to treatment, another 3 cycles (12 weeks) of treatment will be given (6 cycles total). During these additional 3 cycles of therapy, you will have blood drawn (about 2 tablespoons) once a week for routine blood tests.

After 6 cycles of treatment, you will have a physical exam and have around 2 tablespoons of blood drawn for routine blood tests.

Around 3-6 months after you receive your last treatment cycle, you will have a physical exam and blood tests (about 2 tablespoons). After that, you will have a physical examination and blood tests (about 2 tablespoons) every 6 months for the next 2 years. If your disease returns or if you start on more treatment, you will not need to return for these visits. However, you should inform the study doctor/staff that you are receiving other treatment.

If at any time during the study the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

This is an investigational study. All of the drugs used in the study are FDA approved and commercially available. As many as 80 patients will take part in the study. All will be enrolled at M. D. Anderson.

Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

A Phase II Study of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)

Overall (OR) is the total number of participants with any response: Complete remission (CR), is defined as \> 30% lymphocytes in the bone marrow, recovery of blood counts and no clinical symptoms; Nodular partial remission (NPR), is the same as CR but with nodules; Partial remission (PR) is \> 50% decrease of clinical symptoms from baseline and recovery from blood counts.

Bayer

M.D. Anderson Cancer Center

CFAR

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

William G. Wierda, MD, PhD, BS / Associate Professor

Complete remission (CR)

Nodular partial remission (NPR)

Partial remission (PR)

Number of Participants With an Overall Response

Overall Study

Behaviors and Mental Disorders

Disease Progression

Quality of Life

Chromosome 17p Deletion

Venetoclax

Venetoclax was administered orally once daily (QD) for a planned duration of up to 2 years or until disease progression; median time on treatment was 127 weeks. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.

Venetoclax tablets were to be taken orally once daily with a meal and water in the morning at approximately the same time each day. Tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.

ABBVIE INC.

The purpose of this open-label, single-arm study was to evaluate the impact of venetoclax on the quality of life of participants including those with with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL; a type of cancer affecting the blood and the bone marrow) with or without the 17p deletion or TP53 mutation, including participants with an unknown status, as well as R/R CLL participants who had been previously treated with B-cell receptor inhibitor (BCRi) therapy. The starting dose of venetoclax was 20 mg once daily. The dose must have been gradually increased over a period of 5 weeks up to the daily dose of 400 mg. Participants may have continued receiving venetoclax for up to 2 years. After the treatment period, participants may have continued on into a 2-year follow-up period.

A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent).

Open-Label, Single Arm, Phase 3b, Multi-Center Study Evaluating the Impact of Venetoclax on the Quality of Life of Relapsed/Refractory Subjects With Chronic Lymphocytic Leukemia (CLL) (VENICE II)

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the global health status/quality of life scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a physical functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the physical functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a role functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the role functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an emotional functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the emotional functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a cognitive functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the cognitive functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a social functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the social functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a fatigue scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the fatigue scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a nausea and vomiting scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the nausea and vomiting scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a pain scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the pain scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a dyspnea scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the dyspnea scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an insomnia scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the insomnia scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an appetite loss scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the appetite loss scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a constipation scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the constipation scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a diarrhea scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the diarrhea scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a financial difficulties scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the financial difficulties scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the fatigue scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the treatment side effects scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the disease effects scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the infection scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the social problems scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the future health scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change.

The EQ-5D 5L measures quality of life in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on five levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems), and a separate visual analog scale (VAS). Participants rated their health on a vertical visual analogue scale, where the endpoints were labelled 100, "The best health you can imagine" and 0, "The worst health you can imagine". Positive values indicate improvement from baseline.

The EQ-5D 5L measures quality of life in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on five levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems), and a separate visual analog scale (VAS). The scores for the 5 dimensions are used to compute a single utility index score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual, with '0' defined as a health state equivalent to being dead and '1' is full health. The higher the score the better the health status. Positive values indicate improvement from baseline.

Complete remission rate (CR + CRi) is defined as the percentage of participants achieving a CR or CRi as their best response (per the investigator assessment) based on 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria.

ORR is defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or confirmed partial remission (PR) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria as assessed by investigator using the best response at any time during the study.

DoR is defined as the number of days from the date of first response (complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or confirmed partial remission (PR) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria to the earliest date of progressive disease (PD) or death. DOR was analyzed by Kaplan-Meier (K-M) methodology.

TTP is defined as the number of days from the date of first dose of venetoclax to the date of earliest disease progression (PD). TTP was analyzed by Kaplan-Meier (K-M) methodology.

PFS is defined as the number of days from the date of first dose of venetoclax to the date of earliest disease progression (PD) or death. PFS was analyzed by Kaplan-Meier methodology.

OS is defined as the number of days from the date of first dose of venetoclax to the date of death. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later. OS was estimated using Kaplan-Meier methodology.

AbbVie

Age, Continuous

White

Black or African American

Asian

American Indian or Alaska Native

Native Hawaiian or other Pacific Islander

Other

Race/Ethnicity, Customized

All enrolled participants who received at least one dose of venetoclax

Global Medical Services

All enrolled participants who received at least one dose of venetoclax with available data

Mean Change From Baseline to Week 48 in Global Health Status/Quality of Life (GHS/QoL) Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Week 4

Week 8

Week 12

Week 24

Week 36

Week 48

Week 60

Week 72

Week 84

Week 96

Week 108

Final visit

Mean Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Physical Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Role Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Emotional Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Cognitive Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Social Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Fatigue Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Nausea and Vomiting Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Pain Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Dyspnea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Insomnia Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Appetite Loss Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Constipation Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Diarrhea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Financial Difficulties Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

Mean Change From Baseline in Fatigue Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)

Mean Change From Baseline in Treatment Side Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)

Mean Change From Baseline in Disease Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)

Mean Change From Baseline in Infection Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)

Mean Change From Baseline in Social Problems Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)

Mean Change From Baseline in Future Health Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)

Final Visit

Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale Score

Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Health Index Score

Complete Remission Rate (Complete Remission [CR] + Complete Remission With Incomplete Marrow Recovery [CRi])

All enrolled participants who received at least one dose of venetoclax; participants who did not respond were considered non-responders

Overall Response Rate (ORR)

All enrolled participants who received at least one dose of venetoclax, had active disease at baseline, and achieved a response of PR or better

Duration of Overall Response (DOR)

Time to Progression (TTP)

Progression-Free Survival (PFS)

Overall Survival (OS)

Subjects participating in this study will receive a course of three infusions of 3x10\^8 ISF35-transduced cells at periods of not less than 14 days apart followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) at monthly intervals.

ISF35

Januario Castro, MD

The study is a Phase 1b open label, non-randomized, single institution clinical trial that is designed to evaluate the safety and tolerability of three repeat infusions of ISF35 followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) in subjects with refractory, resistant, and/or 17p- CLL.

ISF35 has already been used in two Phase I clinical trials. The trials demonstrated that ISF35 treatment is well tolerated and patients did not experience any significant or unexpected adverse events. Patients reported flu-like symptoms from ISF35, which disappeared within one to three days.

The trials also showed that ISF35 stimulates the immune system to act against CLL cells and sensitize leukemic cells to subsequent treatment. Repeat infusions of ISF35 administered as a single agent to subjects with CLL resulted in durable reductions in circulating and lymph-node bound leukemic cells. Furthermore, CLL patients with 17p deletion responded to standard courses of FCR after receiving ISF35 and achieved durable remissions.

ISF35 is an abbreviation for Immune Stimulatory Factor 35, an offspring of technology discovered by Dr. Thomas J. Kipps, MD, PhD, Professor, Department of Medicine and Deputy Director for Research,UCSD Moores Cancer Center.

A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL

A Phase 1b Study of Repeated Doses of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35) in Combination With Fludarabine, Cyclophosphamide and Rituximab (FCR) in Subjects With Chronic Lymphocytic Leukemia (CLL)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)	NCT01082939	Chronic Lymphoc...	Fludarabine Cyclophosphamid... Alemtuzumab Rituximab	-	M.D. Anderson Cancer Center
A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent).	NCT02980731	Chronic Lymphoc...	Venetoclax	18 Years - 99 Years	AbbVie
A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL	NCT00772486	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.
A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL	NCT00772486	Chronic Lymphoc...	ISF35	18 Years -	Memgen, Inc.
Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)	NCT01082939	Chronic Lymphoc...	Fludarabine Cyclophosphamid... Alemtuzumab Rituximab	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for refractory cll