Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT01886859 | Completed Phase 1

• 9 other identifiers: NCI-2013-0088813-011012-1649254P30CA046934P50CA140158U01CA076576UM1CA186688UM1CA186712
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of lenalidomide when given together with ibrutinib in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with ibrutinib may work better in treating chronic lymphocytic leukemia or small lymphocytic lymphoma.

Conditions

Recurrent B-Cell Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of lenalidomide when combined with ibrutinib

  Defined as the highest dose in which less than or equal to 1/6 patients have dose limiting toxicity. Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patient safety information collected will be summarized using descriptive statistics (number of non-missing values, mean, median, standard deviation, minimum and maximum) for continuous variables and counts and percentages for categorical variables, where applicable.

  28 days

Secondary Outcomes (2)

• Response rates

  Up to 12 months

• Remission/response duration

  Up to 90 days

Other Outcomes (4)

• Non-compartmental areas under the curve (AUCs) for ibrutinib

  Up to day 1 of cycle 2

• Ability of ibrutinib to bind to its targets

  Up to day 1 of cycle 2

• Percentage of occupancy

  Up to day 1 of cycle 2

Study Arms (1)

Treatment (ibrutinib and lenalidomide)

EXPERIMENTAL

Patients receive a run-up cycle of ibrutinib PO daily on days 1-28. Patients then receive ibrutinib PO and lenalidomide PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 12 cycles, patients who have achieved CR/CRi, nodular PR, partial remission with persistent lymphocytosis, partial remission, or who have stable disease discontinue lenalidomide and continue ibrutinib.

Drug: Ibrutinib; Drug: Lenalidomide

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib and lenalidomide)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (ibrutinib and lenalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a diagnosis of CLL/SLL or B-cell prolymphocytic leukemia, as defined by the World Health Organization (WHO)
• During dose escalation, patients must have received at least one prior therapy, need additional cytoreduction, and meet criteria for relapsed or refractory disease; relapsed disease is defined as a patient who previously achieved a CR or a PR, but after a period of six or more months demonstrates evidence of disease progression; refractory disease is defined as progression within six months of the last anti-leukemic therapy, or any response less than a CR or PR; patients who are previously untreated, and do not wish to receive chemotherapy or immunotherapy, are eligible for the dose expansion portion of the study
• Patients may have not received treatment for 28 days before the first day of the study protocol (dose escalation only)
• Estimated life expectancy greater than two months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Ability to understand and willingness to sign a written informed consent document
• Patients must have acceptable organ and marrow function, which should be present independent of growth factor or transfusion support for at least 7 days prior to first dose of study drug, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoeitin which require a 14-day period between dosing and first dose of study drug
• Absolute neutrophil count (ANC) \>= 750 cells/uL (0.75 x 10\^9/L)
• Platelets \>= 50,000 cells/uL (50 x 10\^9/L)
• Hemoglobin \> 8 mg/dL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) unless Gilbert's syndrome or disease infiltration of the liver is present
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x ULN
• Creatinine \< 2.0 x ULN or creatinine clearance (estimated \[est.\] glomerular filtration rate \[GFR\] \[Cockcroft-Gault\]) \>= 30 mL/min
• Prothrombin time (PT)/international normalized ratio (INR) \< 1.5 x ULN and partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT) \< 1.5 x ULN
• The effects of ibrutinib on the developing human fetus are unknown; lenalidomide is likely to be teratogenic; therefore, females of childbearing potential (FCBP) must have a negative pregnancy test (sensitivity of at least 25 mIU/mL) performed once before ibrutinib and a total of two negative tests before initiating lenalidomide; a FCBP is a female who: 1) has achieved menarche at some point; 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); the pre-ibrutinib pregnancy test will be initiated at enrollment; the first pre- lenalidomide test will be performed within 10-14 days of starting lenalidomide (cycle 0, day 15), and the second pre-lenalidomide test (3rd total test) will be within 24 hours of the first dose of lenalidomide; the patient may not receive lenalidomide until the study doctor has verified that the results of these pregnancy tests are negative; pregnancy tests (if applicable) are then to be conducted weekly during the first month, and monthly thereafter in women with a regular menstrual cycle, as well as at study discontinuation, and at day 28 following study discontinuation; if menstrual cycles are irregular, pregnancy testing will be conducted weekly for the first month, and then every 14 days while on the study, at study discontinuation, and at days 14 and 28 following study drug discontinuation; pregnancy testing and counseling are to be performed if a patient misses her period or if there is any abnormality in menstrual bleeding; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; further, FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; male and female patients must agree to use highly effective methods of birth control (e.g. condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug; all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

You may not qualify if:

• Prior therapy with Bruton's tyrosine kinase (BTK) inhibitor
• Concurrent treatment with other investigational or anti-neoplastic agents
• Patients requiring daily corticosteroids at a prednisone equivalent of \> 20 mg daily should not be enrolled; if corticosteroids can be discontinued (or reduced to \< 20 mg per day of prednisone or equivalent), the discontinuation or dose reduction should be done at least 7 days prior to first dose
• Chemotherapy =\< 21 days prior to first administration of study treatment and/or monoclonal antibody =\< 6 weeks prior to first administration of study treatment; immunotherapy, radiotherapy or experimental therapy within 28 days of first day of study drug dosing, or within six weeks of first day of study drug dosing in the event that nitrosoureas or mitomycin were used; concurrent systemic immunosuppressant therapy other than corticosteroids (e.g. cyclosporine A, tacrolimus, etc) must be discontinued within 28 days of the first dose of study drug
• Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or any class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction, unstable angina or acute coronary syndrome within 6 months prior to on-study registration
• Uncontrolled psychiatric illness that would limit compliance with study requirements
• Central nervous system disease involvement; these patients should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of prior malignancy, with the exception of the following:
• Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening, and felt to be at low risk for recurrence by treating physician
• Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
• Adequately treated cervical carcinoma in situ without current evidence of disease
• Serologic status reflecting active hepatitis B or C infection; patients that are hepatitis B core antibody, hepatitis B surface antigen (HBsAg) or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment; PCR positive patients will be excluded
• Active infection at initiation of study; recent infections requiring systemic treatment need to have completed therapy \> 14 days before the first dose of study drug
• Major surgery within 4 weeks or minor surgery within 7 days of the first day of study drug dosing
• Unable to swallow capsules or disease significantly affecting gastrointestinal function or resection of the stomach or small bowel, or symptomatic inflammatory bowel disease or ulcerative colitis or partial or complete bowel obstruction

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Prolymphocytic, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Prolymphocytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Daniel A Pollyea

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2013
• First Posted: June 26, 2013
• Study Start: April 26, 2013
• Primary Completion: November 15, 2020
• Study Completion: September 21, 2022
• Last Updated: September 26, 2022

Record last verified: 2022-09

Locations

US (3)