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Lymphoma, Non-HodgkinPhase 1NCT04434196

A Safety and Preliminary Efficacy Study of CC-99282 in Combination With Obinutuzumab in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase 1 study testing CC-99282 and Obinutuzumab in people with Lymphoma, Non-Hodgkin, run by Celgene at 15 sites in 4 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

CC-99282-CLL-001 study is a Phase IB dose escalation and expansion clinical study of CC-99282 administered in combination with Obinutuzumab in subjects with relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
CC-99282 and Obinutuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
15 sitesin 4 countries
Study dates
21 Dec 2020to 21 May 2024
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

  • Subject is ≥18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Must have a documented diagnosis of CLL/SLL requiring treatment (IwCLL Guidelines for the Diagnosis and Treatment of CLL). In addition presence of clinically measurable disease determined by at least one of the factors listed:
  • nodal lesion that measures ≥ 1.5 cm in longest dimension (LD) and ≥ 1.0 cm in longest perpendicular dimension (LPD), or
  • spleen that measures ≥ 14 cm in longest vertical dimension (LVD) with a minimum of 2 cm enlargement, or
  • liver that measures ≥ 20 cm in LVD with a minimum of 2 cm enlargement, or
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  • peripheral blood B lymphocyte count > 5000/uL
  • All eligible subjects must be relapsed after or be refractory to >2 prior lines of therapy one of which must have included an approved BTK inhibitor.
  • Must meet the following laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3 or ≥ 1000 cells/mm^3 if secondary to bone marrow involvement by disease, without growth factor support for 7 days (14 days if pegfilgastrim).
  • Platelet count ≥ 75,000 cells/mm^3 (100 x 10^9/L) or ≥ 50,000 cells/mm^3 (50 x 10^9/L) if secondary to bone marrow involvement by disease, without transfusion for 7 days.
  • Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) < 3.0 x upper limit of normal (ULN).
  • Serum bilirubin < 1.5 x ULN unless due to Gilbert's syndrome.
  • Calculated creatinine clearance of ≥ 60 ml/min.

Who cannot join

  • Presence of any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • Prior allogeneic stem cell transplant (SCT)/bone marrow transplant within 12 months of signing the ICF. Subjects who received allogeneic SCT ≥ 12 months before signing the ICF may be eligible provided there is no ongoing graft-versus-host disease and no ongoing immune suppression therapy.
  • Subject has received prior CAR-T or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to starting CC-99282.
  • Subject has received prior therapy with CRBN-modulating drug (eg, lenalidomide, avadomide/CC-122, pomalidomide) ≤ 4 weeks prior to starting CC-99282.
  • History of second malignancies with life expectancy of ≤ 2 years or requirement of therapy that would confound study results.
  • Peripheral neuropathy ≥ Grade 2.
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  • History of hypersensitivity to lenalidomide, pomalidomide, thalidomide.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management.
  • Active disease transformation (ie, Richter's Syndrome)
  • Uncontrolled/active autoimmune hemolytic anemia or thrombocytopenia

Trial locations and contacts

15 sites in 4 countries.

15 sites in 4 countries

Spain6 sites

  • Local Institution - 302

    Barcelona, 08035

  • Local Institution - 306

    Madrid, 28027

  • Local Institution - 301

    Madrid, 28041

  • Local Institution - 304

    Pamplona, Navarre, 31008

  • Local Institution - 303

    Salamanca, 37007

  • Local Institution - 305

    Valencia, 46010

Other trials in Spain

United States4 sites

  • Local Institution - 106

    Boston, Massachusetts, 02215

  • Local Institution - 104

    Columbus, Ohio, 43210

  • Local Institution - 107

    Dallas, Texas, 75390

  • Local Institution - 101

    Portland, Oregon, 97201-3098

Other trials in United States

Austria3 sites

  • Local Institution - 403

    Innsbruck, 6020

  • Local Institution - 401

    Salzburg, 5020

  • Local Institution - 402

    Vienna, 1090

Other trials in Austria

Canada2 sites

  • Local Institution - 202

    Montreal, Quebec, H3T 1E2

  • Local Institution - 201

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 1B, Multicenter, Open-label Study to Determine the Safety, Pharmacokinetics and Preliminary Efficacy of CC-99282 in Combination With Obinutuzumab in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

CC-99282-CLL-001 study is a Phase IB dose escalation and expansion clinical study of CC-99282 administered in combination with Obinutuzumab in subjects with relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Read the detailed description

All eligible subjects must be relapsed or refractory to at least 2 prior lines of therapy, one of which must have included an inhibitor of B-cell receptor signaling (approved Bruton's tyrosine kinase inhibitor [BTKi] or Phosphoinositide 3-kinase inhibitor [PI3Ki]) or venetoclax. The dose escalation (Part A) will evaluate the safety, tolerability, and PK of escalating doses of CC-99282 given in combination with intravenous obinutuzumab to determine the MTD and RP2D of CC-99282 when given in combination with obinutuzumab. The dose expansion (Part B) may occur at the MTD established in the dose escalation phase, or at an alternative tolerable dosing schedule, based on review of safety, PK and PD data from Part A.

Being tested
CC-99282, Obinutuzumab
Keywords
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Safety, Efficacy, CC-99282, Obinutuzumab, Relapsed, Refractory
Medical subject headings
Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence

What participants receive

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

Study groups in NCT04434196
Study groupRoleWhat they receive
CC-99282 + obinutuzumabExperimentalEscalating doses of CC-99282 administered orally once daily on intermittent schedules with obinutuzumab IV infusion 1000 mg up to 2 years in Part A. CC-99282 administered orally once daily at MTD or alternative tolerating dosing schedule with obinutuzumab IV infusion 1000 mg up to 2 years in Part B.
Receives: Drug: CC-99282; Drug: Obinutuzumab

What is being measured

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

  1. Dose Limiting Toxicity (DLT)

    Number of subjects with a DLT

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days)

  2. Maximum tolerated dose (MTD)

    The highest dose of CC-99282 in combination with obinutuzumab associated with acceptable safety and tolerability

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days

  3. Adverse Events (AEs)

    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

    Measured: From first subjects first visit until 28 days after last subject discontinued study treatment

Secondary outcomes (14)

  1. Pharmacokinetics - Cmax

    Maximum observed plasma concentration

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days)

  2. Pharmacokinetics - AUC

    Area under the plasma concentration-time curve

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days)

  3. Pharmacokinetics - Tmax

    Time to Cmax

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days)

  4. Pharmacokinetics - T-HALF

    Terminal-phase elimination half-life

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days)

  5. Pharmacokinetics - CLT/F

    Apparent total clearance of the drug from plasma after oral administration

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days)

  6. Pharmacokinetics - Vz/F

    Apparent volume of distribution during terminal phase after non-intravenous administration

    Measured: Up to Cycle 2 Day 14 (each cycle is 28 days)

  7. Objective response rate (ORR)

    Sum of complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), partial response (PR), partial response with lymphocytosis (PRL) determined by iwCLL criteria

    Measured: Up to approximately 3 years

  8. Duration of response (DoR)

    Time from first documentation of response (≥ PR) to the first documentation of PD or death

    Measured: Up to approximately 3 years

  9. Progression free survival

    Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause

    Measured: Up to approximately 3 years

  10. Overall survival

    Time from first dose of CC-99282 to death from any cause

    Measured: Up to approximately 3 years

  11. Complete response with incomplete marrow recovery (CRi)

    As assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

    Measured: Up to approximately 3 years

  12. Nodular partial response (nPR)

    As assessed by iwCL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

    Measured: Up to approximately 3 years

  13. Partial response (PR)

    As assessed by iwC and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

    Measured: Up to approximately 3 years

  14. Partial response with lymphocytosis (PRL)

    As assessed by iwCLL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

    Measured: Up to approximately 3 years

Timeline

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

  1. First posted16 Jun 2020
  2. Study start21 Dec 2020
  3. Primary completion21 May 2024
  4. Study completion21 May 2024

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
Sequential
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04434196
Sponsor's protocol ID
CC-99282-CLL-001
Other IDs
U1111-1251-4261, 2019-003228-18, 2019
Status last verified
Jul 2024
First submitted
1 Jun 2020
Last updated
25 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CC-99282 and Obinutuzumab in people with Lymphoma, Non-Hodgkin, run by Celgene at 15 sites in 4 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 14 inclusion and 11 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 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Spain, United States, Austria, Canada. 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?

Dose Limiting Toxicity (DLT) (time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)). The study lists 3 primary outcomes in all. 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 NCT04434196.

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 25 Jul 2024.

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