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Indolent B-Cell Non-Hodgkin LymphomaPhase 1NCT04578600

CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma

A Phase 1 study testing Lenalidomide, Obinutuzumab and Oral Azacitidine in people with Indolent B-Cell Non-Hodgkin Lymphoma and Recurrent B-Cell Non-Hodgkin Lymphoma, run by Joseph Tuscano at 1 site in United States.

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 phase I/Ib trial investigates the side effects of CC-486 and how well it works in combination with lenalidomide and obinutuzumab in treating patients with CD20 positive B-cell lymphoma that has come back (recurrent) or has not responded to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lenalidomide, Obinutuzumab and Oral Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
23 Oct 2020to 21 Feb 2025
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

  • Previously treated, histologically confirmed CD20+ B cell lymphoma which includes mantle cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, hairy cell leukemia, marginal zone lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, and lymphoplasmacytic lymphoma. Fine needle aspirates are not acceptable
  • Ability to understand and willingness to sign an informed consent form
  • Ability to adhere to the study visit schedule and other protocol requirements
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, or Karnofsky performance status (KPS) performance status of 60% or greater
  • Life expectancy >= 3 months
  • Leukocytes >= 3,000/uL
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  • Absolute neutrophil count >= 1,000/uL
  • Platelets >= 50,000/uL
  • Total bilirubin: =< 2.0 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
  • Serum creatinine
  • =< 2.0 x ULN, OR
  • Calculated creatinine clearance >= 30 ml/min/1.73 M^2 by the modified Cockcroft and Gault Formula, OR
  • Creatinine clearance >= 30 mL/min obtained from a 24-hour urine collection
  • At least one measurable lesion according to International workshop lymphoma response criteria. There must be measurable lymphadenopathy to follow with serial exam and/or imaging
  • All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
  • Submission of original biopsy for review and verification by participating center hematopathologist
  • Disease free of prior malignancies for >= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program, and be willing and able to comply with the requirements of the REMS program
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. (Subjects intolerant to acetylsalicylic acid [ASA] may use low molecular weight heparin)
  • Must be able to swallow study drugs
  • Human immunodeficiency virus (HIV) infected patients are eligible provided they meet all the other eligibility criteria of the study in addition to the following:
  • No history of acquired immunodeficiency syndrome (AIDS)-defining conditions other than lymphoma or history of CD4+ T-cells below 200/mm^3 prior to beginning combination antiretroviral therapy (cART)
  • After HIV diagnosis and during treatment with cART, patients should have maintained CD4+ T-cells >= 350/mm^3 prior to lymphoma diagnosis. Patents who never immune reconstituted to a stable level above 350/mm^3 are not eligible
  • At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to >= 250/mm^3
  • At the time of study entry the HIV viral load must be undetectable by standard laboratory assay
  • During prior lymphoma therapy, patients must not have experienced documented infections attributed to the HIV+ status
  • No history of non-adherence to cART and willing to adhere to cART while on study
  • Antiretroviral drugs with overlapping or similar toxicity profiles as study agents not allowed:
  • Efavirenz not allowed due to potential central nervous system (CNS) toxicity
  • Stavudine not allowed due to potential neuropathic effects
  • Zidovudine not allowed due to myelosuppressive effects
  • Patients must be willing to be followed at a minimum of approximately every 3 months by physician expert in HIV disease management

Who cannot join

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Known hypersensitivity to lenalidomide, thalidomide, obinutuzumab, or mannitol
  • A history of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Any prior use of obinutuzumab or CC-486
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  • Concurrent use of other anti-cancer agents or treatments
  • Known active hepatitis B or C. Patients on suppressive therapy with a negative viral load and no evidence of hepatic damage are eligible
  • Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
  • Active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. A history of hemolytic anemia associated with the lymphoma does not exclude a patient from the study
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking azacitidine)
  • For CC-486: History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug (CC-486) and/or predispose the subject to an increased risk of gastrointestinal toxicity
  • Abnormal coagulation parameters (prothrombin time [PT] > 15 seconds, partial thromboplastin time [PTT] > 40 seconds, and/or international normalized ratio [INR] > 1.5)
  • Significant active cardiac disease within the previous 6 months including:
  • New York Heart Association (NYHA) class 4 congestive heart failure (CHF)
  • Unstable angina
  • Myocardial infarction

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: A Phase I/IB Pilot Study of CC-486 Combined With Lenalidomide and Obinutuzumab for Relapsed/Refractory Indolent B-Cell Lymphoma

This phase I/Ib trial investigates the side effects of CC-486 and how well it works in combination with lenalidomide and obinutuzumab in treating patients with CD20 positive B-cell lymphoma that has come back (recurrent) or has not responded to treatment (refractory). Chemotherapy drugs, such as CC-486, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lenalidomide is a drug that alters the immune system and may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Obinutuzumab is a type of antibody therapy that targets and attaches to the CD20 proteins found on follicular lymphoma cells as well as some healthy blood cells. Once attached to the CD20 protein the obinutuzumab is thought to work in different ways, including by helping the immune system destroy the cancer cells and by destroying the cancer cells directly. Giving CC-486 with lenalidomide and obinutuzumab may improve response rates, quality, and duration, and minimize adverse events in patients with B-cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVE:

To assess the safety and toxicity of oral azacitidine (CC-486) in combination with lenalidomide and obinutuzumab.

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of CC-486 in combination with lenalidomide and obinutuzumab in subjects with relapsed/refractory indolent B-cell lymphoma as assessed by:

Ia. Overall response rate: complete response (CR) + partial response (PR) per 2016 Lugano criteria and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.

Ib. Duration of response (DOR): will be calculated from time of initial response assessment demonstrating at least PR until disease response assessment that demonstrates progressive disease.

Ic. Time to response (TTR): calculated as time from registration to first disease response assessment that demonstrates at least PR.

Id. Progression-free survival (PFS): Patients are considered a failure for this endpoint if they die or if they relapse/progress or receive additional anti-lymphoma therapy.

Ie. Determine the recommended phase 2 dose (RP2D).

Being tested
Lenalidomide, Obinutuzumab, Oral Azacitidine
Medical subject headings
Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Leukemia, Hairy Cell, Lymphoma, Mantle-Cell

What participants receive

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

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • ObinutuzumabBiological

    Also called Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva

    Given IV

  • Oral AzacitidineDrug

    Also called CC-486

    Given PO

Study groups in NCT04578600
Study groupRoleWhat they receive
Treatment (lenalidomide, oral azacitidine, obinutuzumab)ExperimentalPatients receive azacitidine PO QD on days 1-21, obinutuzumab IV over on days 8, 15, 22, and 29, and lenalidomide PO QD on days 8-28 of cycle 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Patients then receive azacitidine PO QD on days 1-21, obinutuzumab IV over on day 1, and lenalidomide PO QD on days 1-21. Cycles repeats every 28 days in the absence of disease progression, unacceptable toxicity, or until stem cell transplant. Patients who achieve SD, PR, or CR do not proceed to stem cell transplant may continue treatment for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Lenalidomide; Biological: Obinutuzumab; Drug: Oral Azacitidine

What is being measured

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

  1. Incidence of adverse events (AEs)

    Safety summaries will include tabulations in the form of tables and listings. The frequency (number and percentage) of treatment-emergent AEs will be reported. The frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions will be reported. Additional AE summaries will include AE frequency by AE severity and by relationship to study drug. Toxicity data by type and severity will be summarized by frequency tables. Per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.

    Measured: Up to 30 days post-last dose

Secondary outcomes (9)

  1. Complete response rate

    Response will be assessed based on Cheson, Lugano classification 2016. The number and percentage of subjects with a complete response at 120 weeks will be tabulated.

    Measured: At 48 weeks

  2. Overall response rate (ORR) (complete response + partial response)

    Will be assessed by the investigator based on Cheson, Lugano classification 2016. The number and percentage of subjects with an ORR will be tabulated. The best ORR will be recorded.

    Measured: Up to 2 years

  3. Duration of response

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the time by which measurement criteria for complete response or partial response, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 2 years

  4. Time to response

    Comparison by important subgroups will be made using the log-rank test. Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From registration to first disease response assessment that demonstrates at least partial response, assessed up to 2 years

  5. Progression-free survival

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the date of first dose (cycle 1, day 1) to the date of first documented progression or death, assessed up to 2 years.

  6. Recommended phase 2 dose

    The maximum tolerated dose (MTD) will be defined as the highest dose of CC-486 tested in which fewer than 33% of patients experience a dose-limiting toxicity and at least 6 patients have been treated at that dose. The MTD will be the recommended phase 2 dose, provided that other safety considerations are acceptable.

    Measured: Up to 35 days

  7. Time to next treatment

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the end of cycle 24 (each cycle is 28 days) to the date of first documented new anti-lymphoma treatment, assessed up to 2 years.

  8. Event-free survival

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the date of first dose (cycle 1, day 1) to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death, assessed up to 2 years.

  9. Overall survival

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the date of first dose (cycle 1, day 1) to the date of death regardless of cause, assessed up to years.

Timeline

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

  1. First posted8 Oct 2020
  2. Study start23 Oct 2020
  3. Primary completion12 Dec 2023
  4. Study completion21 Feb 2025

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04578600
Sponsor's protocol ID
1548998
Other IDs
NCI-2020-05946, UCDCC#282, P30CA093373
Status last verified
Apr 2025
First submitted
21 Sep 2020
Last updated
24 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lenalidomide, Obinutuzumab and Oral Azacitidine in people with Indolent B-Cell Non-Hodgkin Lymphoma and Recurrent B-Cell Non-Hodgkin Lymphoma, run by Joseph Tuscano at 1 site in United States.

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 34 inclusion and 18 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 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Incidence of adverse events (AEs) (time frame: Up to 30 days post-last dose). 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 NCT04578600.

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 24 Apr 2025.

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