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Alkylating agents

Venetoclax + Obinutuzumab for Leukemia (CRISTALLO Trial)

Phase 3

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm

CLL requiring treatment according to the iwCLL criteria

Must not have

Known central nervous system involvement

Radiotherapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up arm ven + g: day 1 of cycle 1-12, day 28 after treatment completion/early termination (tc/et), follow up (fu) visits; arm fcr/br: day 1 of cycle 1-6, day 28 after tc/et, end of combination treatment response visit and fu visit (up to 74 months)

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial will compare the efficacy and safety of two different treatments for previously untreated CLL without DEL(17P) or TP53 mutation. One treatment group will receive venetoclax and obinutuzumab, and the other will receive fludarabine + cyclophosphamide + rituximab or bendamustine + rituximab.

Who is the study for?

This trial is for adults over 18 with untreated Chronic Lymphocytic Leukemia (CLL) who are fit (CIRS score ≤6, creatinine clearance ≥70 mL/min), and have a life expectancy of more than 6 months. They must not be pregnant or nursing, agree to use contraception, and should not have certain infections or recent drug treatments that could interfere with the study.

What is being tested?

The trial compares Venetoclax plus Obinutuzumab against Fludarabine, Cyclophosphamide plus Rituximab or Bendamustine plus Rituximab in treating CLL. Participants will be randomly assigned to one of these two treatment groups to assess effectiveness and safety.

What are the potential side effects?

Potential side effects include digestive issues, low blood cell counts leading to increased infection risk, fatigue, liver function abnormalities. There's also a chance of allergic reactions due to medication components.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I agree to either not have sex or use birth control, and not donate sperm.

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My CLL condition requires treatment.

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I am 18 years old or older.

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I have chronic lymphocytic leukemia that has not been treated yet.

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My white blood cell count is healthy, unless my bone marrow is affected.

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My overall health score is good and my kidneys are working well.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer has spread to my brain or spinal cord.

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I am currently undergoing or have completed radiotherapy.

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I have received treatments for lymphoma or leukemia.

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I have been diagnosed with Small Lymphocytic Lymphoma (SLL) only.

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I do not have HIV or HTLV-1.

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I have had progressive multifocal leukoencephalopathy in the past.

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I have had cancer before.

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I haven't taken strong or moderate CYP3A affecting drugs in the last week.

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My CLL has transformed into a more aggressive form of lymphoma.

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I have an uncontrolled autoimmune blood condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ arm ven + g: day 1 of cycle 1-12, day 28 after treatment completion/early termination (tc/et), follow up (fu) visits; arm fcr/br: day 1 of cycle 1-6, day 28 after tc/et, end of combination treatment response visit and fu visit (up to 74 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~arm ven + g: day 1 of cycle 1-12, day 28 after treatment completion/early termination (tc/et), follow up (fu) visits; arm fcr/br: day 1 of cycle 1-6, day 28 after tc/et, end of combination treatment response visit and fu visit (up to 74 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and arm ven + g: day 1 of cycle 1-12, day 28 after treatment completion/early termination (tc/et), follow up (fu) visits; arm fcr/br: day 1 of cycle 1-6, day 28 after tc/et, end of combination treatment response visit and fu visit (up to 74 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQC-30)

Change From Baseline in M.D. Anderson Symptom Inventory-CLL (MDASI-CLL) Score

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471

33%

Neutropenia

11%

SARS-CoV-2 test positive

11%

Sepsis

11%

Abdominal pain

11%

Pneumonia

11%

Rhinovirus infection

11%

COVID-19

11%

Gastroenteritis

11%

Pneumonia pseudomonal

11%

Electrocardiogram QT prolonged

11%

Anaemia

11%

Neutrophil count decreased

11%

Hypokalaemia

11%

Febrile neutropenia

11%

Supraventricular tachycardia

11%

Blood creatinine increased

11%

White blood cell count decreased

11%

Dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

Bendamustine + Rituximab Crossover Substudy

Venetoclax + Rituximab Re-Treatment Substudy

Venetoclax + Rituximab Main Study

Bendamustine + Rituximab Main Study

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: VEN + GExperimental Treatment2 Interventions

Participants will receive 12 cycles of treatment (each cycle is 28 days). Venetoclax (VEN) will be administered orally, daily, with a 5-week ramp-up period, starting on Cycle 1, Day 22 and administration will continue until the end of Cycle 12. Obinutuzumab (G) will be administered intravenously (IV) on Days 1 (and 2), 8, and 15 of Cycle 1 and on Day 1 of Cycles 2-6.

Group II: FCR/BRActive Control4 Interventions

Participants will receive 6 cycles of Fludarabine + Cyclophosphamide + Rituximab (FCR) consisting of a single cycle of a single infusion of rituximab on Day 1 and fludarabine and cyclophosphamide infusions on Days 1-3 of each 28-day cycle or bendamustine (B) as infusions on Days 1 and 2 and a single cycle of rituximab on Day 1 of each 28-day cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Obinutuzumab

2014

Completed Phase 3

~3470

Venetoclax

2019

Completed Phase 3

~2200