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Leukemia Lymphocytic Chronic B-CellPhase 1NCT01744626

Safety Study of CC-292 and Rituximab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase 1 study testing CC-292 and Rituximab in people with Leukemia Lymphocytic Chronic B-Cell, run by Celgene Corporation at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a dose finding study using a 3 + 3 dose escalation and expansion design to determine a Not Tolerated Dose (NTD), Optimal Biological Effect Dose (OBE) and / or Maximum Tolerated Dose (MTD). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia Lymphocytic Chronic B-Cell
What is being tested?
CC-292 and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
8 sitesin 2 countries
Study dates
Dec 2012to Dec 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female subjects 18 years of age and older at the time of signing the informed consent document.
  • Understand and voluntarily sign an informed consent document (ICD) prior to any study related assessments/procedures being conducted.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Body weight ≥ 50 kg.
  • Must have a documented diagnosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (International Workshop) guidelines for the diagnosis and treatment of CLL (Appendix A), or lymphoma guidelines (Appendix B) for diagnosis and treatment of SLL by investigator assessment.
  • Have failed ≥ 1 previous treatments for CLL/SLL, and have relapsed or refractory disease following last prior treatment.
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  • Refractory is defined as CLL/SLL that does not achieve at least a partial response (PR) to therapy or that progresses within 6 months of treatment. Relapsed CLL/SLL refers to disease that progresses after ≥ 6 months in subjects who had achieved a PR or complete response (CR) to therapy.
  • Subjects must have failed, refused, be ineligible, or not otherwise appropriate, per the investigator's judgment, for autologous stem cell transplant (SCT) unless enrollment in this study is anticipated to debulk lesions in preparation for SCT.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤ 2
  • Life expectancy of at least 3 months form the time of signing the ICD.
  • Females of childbearing potential (FCBP)must have a negative medically supervised pregnancy test prior to starting of study therapy.
  • Male subjects must:
  • Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug treatment, during any dose interruption and for 28 days after end of study therapy.
  • Agree to not donate semen during study drug treatment and for 28 days after end of study drug treatment.
  • Ability to swallow oral capsules without difficulty.
  • Have an echocardiogram or multigated acquisition scan of the heart demonstrating left ventricular ejection fraction (LVEF) ≥ 50% or the institution's lower limit of normal.
  • Have recovered from adverse, toxic effects of prior therapies to Grade ≤ 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI/CTCAE) version 4.03 except for alopecia and peripheral neuropathy. This requirement will be subordinate to specific clinical and laboratory criteria that are otherwise specifically addressed in these inclusion/exclusion criteria.

Who cannot join

  • Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  • Any condition that confounds the ability to interpret data from the study.
  • Autologous stem cell transplant within 3 months of screening date.
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection requiring parenteral antibiotics.
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  • Uncontrolled diabetes mellitus as defined by the investigator.
  • Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart. Association Classification for Heart Disease; AppendixG).
  • Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months of signing the ICD.
  • Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia. Subjects with controlled atrial fibrillation that is asymptomatic are eligible.
  • Pregnant or lactating females.
  • Prior history of malignancies, unless the subject has been free of the disease for ≥ 3 years of signing the informed consent. Exceptions to the ≥ 3 year time limit include history of the following:
  • Basal cell carcinoma of the skin.
  • Squamous cell carcinoma of the skin.
  • Carcinoma in situ of the cervix.
  • Carcinoma in situ of the breast.
  • Carcinoma in situ of the bladder.
  • Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b). (The TNM staging system is based on the extent of the tumor (T), whether cancer cells have spread to nearby (regional) lymph nodes (N), and whether distant (to other parts of the body) metastasis (M) has occurred).
  • Known seropositivity for or history of active viral infection with Human Immunodeficiency Virus (HIV).
  • Seropositive for or active viral infection with Hepatitis B virus (HBV):
  • HBV surface antigen positive.
  • HBV surface antigen negative, HBV surface antibody positive and/or HBV core antibody positive and detectable viral deoxyribonucleic acid (DNA).
  • Note: Subjects who are HBV surface antigen negative and viral DNA negative are eligible.
  • Subjects who had HBV but have received an antiviral treatment and show no detectable viral DNA within 6 months of signing the ICD are eligible.
  • Subjects who exhibit the classical vaccination profile of HBV surface antibody positive, HBV core antibody negative, and HBV surface antigen negative are eligible.
  • Known seropositivity for or active viral infection with Hepatitis C virus (HCV).
  • Subjects who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic event (VTE) prophylaxis.
  • Any of the following laboratory abnormalities:
  • Absolute neutrophil count (ANC) ≤ 1,000 cells/mm3 (1.0 x 109/L) unless secondary to bone marrow involvement by lymphoma as demonstrated by recent bone marrow aspiration and bone marrow biopsy.
  • Platelet count ≤ 50,000/mm3 (50 x 109/L) unless secondary to bone marrow involvement by lymphoma as demonstrated by recent bone marrow aspiration and bone marrow biopsy. Note that growth factors or transfusions should not be administered during screening for the sole purpose of helping a subject exceed these exclusionary laboratory values.
  • Serum Aspartate Transaminase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) or Alanine Transaminase/Serum Glutamic Pyruvate Transaminase (ALT/SGPT) > 3.0 x Upper Limit of Normal (ULN) or > 5.0 x ULN in cases of documented liver involvement by lymphoma.
  • Serum bilirubin > 1.5 x ULN or > 3.0 x ULN in cases of Gilbert's Syndrome and documented liver involvement by lymphoma.
  • Calculated creatinine clearance using the Cockcroft-Gault formula (Cockcroft, 1976).
  • For subjects enrolling in Part 1 creatinine clearance value must be < 30 mL/min
  • For subjects enrolling in Part 2 creatinine clearance value must be < 60 mL/min
  • Corrected QT interval (QTc) prolongation (defined as a QTc > 450 msec for males and > 470 msec for females [Fridericia's correction] echocardiograms (ECGs) or other clinically significant ECG abnormalities as assessed by the investigator. An average of 3 QTc intervals may be obtained if necessary.
  • Evidence of Tumor Lysis Syndrome (TLS) per the Cairo-Bishop definition of laboratory TLS ([Appendix F] subjects may be enrolled upon correction of electrolyte abnormalities).
  • Prior exposure to Bruton Tyrosine Kinase inhibitors.
  • Chemotherapy, radiotherapy, investigational anti cancer therapy or major surgery within 28 days of Day 1 dosing.
  • Use of systemic corticosteroids in doses greater than prednisone equivalent 20 mg/day within 3 weeks prior to the first dose of study drug treatment.
  • Concomitant use of medicines known to cause QT prolongation or torsades de pointes (Appendix I).
  • Chronic use of H2 antagonists or proton pump inhibitors or their use within 7 days of first dose of study drug treatment. Subjects with chronic gastroesophageal reflux disease, dyspepsia, and peptic ulcer disease, should be carefully evaluated for their suitability for this treatment prior to enrollment in this study.
  • Gastrointestinal abnormalities including the ability to take oral medication, require intravenous (IV) alimentation, or prior surgical procedures affecting absorption.
  • History of hypersensitivity reaction to Rituximab.
  • Any vaccinations incorporating the use of a live vaccine within 3 weeks from first dose.

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States4 sites

  • Hackensack UMC

    Hackensack, New Jersey, 07601

  • Clearview Cancer Institute

    Huntsville, Alabama, 35805

  • Horizon Oncology Research, Inc

    Lafayette, Indiana, 47905

  • The West Clinic

    Memphis, Tennessee, 38120

Other trials in United States

Germany4 sites

  • Städt. Klinikum München-Schwabing

    Bayern, 80804

  • Universitatsklinikum Wurzburg

    Bayern, 907080

  • Universitätsklinik Köln

    Cologne, 50924

  • Universitätsklinik Ulm

    Ulm, Bavaria, 89070

Other trials in Germany

About this study

Official title: A Phase 1b, Multi-center, Open Label, Study to Determine the Safety and Activity of CC-292 in Combination With Rituximab in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma.

This is a dose finding study using a 3 + 3 dose escalation and expansion design to determine a Not Tolerated Dose (NTD), Optimal Biological Effect Dose (OBE) and / or Maximum Tolerated Dose (MTD). These data will be used to establish a Recommended Phase 2 Dose (RP2D) for the combination of CC-292 and Rituximab in subjects with CLL.

Read the detailed description

This dose finding study uses a 3 + 3 dose escalation and expansion design to establish the recommended Phase 2 dose (RP2D). Treatment will consist 28 day treatment cycles with a single Rituximab infusion per cycle for 6 cycles and twice daily (days 1-28) administration of CC-292 with a starting dose cohort of 375mg twice a day. Following safety review of the data from the initial cohort and confirmation that the initial dose is tolerable, the next dose level will be enrolled with a once per cycle Rituximab infusion for 6 cycles and twice daily CC-292 at 500 mg.

Determination of the maximum tolerated dose and/or optimal biologic effect will be used to establish a dose for evaluation in an expansion cohort of 24 subjects. Evaluation of the data for subjects in the expansion cohorts will result in establishment of a RP2D.

Being tested
CC-292, Rituximab
Keywords
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Medical subject headings
Leukemia, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CC-292Drug

    Cohort 1: 375 mg CC-292 will be administered twice a day on Days 1-28 Cohort 2: 500 mg CC-292 will be administered twice a day on Days 1-28

  • RituximabDrug

    Cohort 1: Rituximab once per cycle Cohort 2: Rituximab once per cycle

Study groups in NCT01744626
Study groupRoleWhat they receive
CC-292 with RituximabExperimentalDose Escalation
Receives: Drug: CC-292; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse Events

    Number of participants with adverse events

    Measured: Up to a year

Secondary outcomes (7)

  1. PK-Cmax

    Maximum observed plasma concentration

    Measured: Up to 15 days

  2. PK-Tmax

    Time to maximum observed plasma concentration of CC-292 in combination with Rituximab.

    Measured: Up to 15 days

  3. PK-λz

    Terminal phase rate constant.

    Measured: Up to 15 days

  4. PK-t1/2

    Estimate of the terminal phase half-life in plasma.

    Measured: Up to 15 days

  5. PK-AUC (0-t)

    Area under the plasma concentration-time curve from time zero to the last quantifiable time point.

    Measured: Up to 15 days

  6. PK-AUC0-∞

    Area under the plasma concentration time curve from time zero extrapolated to infinity.

    Measured: Up to 15 days

  7. Efficacy

    To evaluate the preliminary efficacy of CC-292 in combination with Rituximab, including Response Rate, Duration of Response and Progression-Free Survival

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2012 (estimated)
  2. Study startDec 2012
  3. Primary completionDec 2015
  4. Study completionDec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01744626
Sponsor's protocol ID
CC-292-CLL-002
Other IDs
2012-003767-21
Status last verified
Apr 2016
First submitted
5 Dec 2012
Last updated
19 Apr 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CC-292 and Rituximab in people with Leukemia Lymphocytic Chronic B-Cell, run by Celgene Corporation at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events (time frame: Up to a year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01744626.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2016.

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