Ibrutinib and Palbociclib in Treating Patients With Previously Treated Mantle Cell Lymphoma

NCT02159755 | Active Not Recruiting Phase 1

• 6 other identifiers: NCI-2014-0120214030148539534K24CA201524UM1CA186704UM1CA186712
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 4

Brief Summary

This phase I trial studies the side effects and best dose of ibrutinib and palbociclib in treating patients with previously treated mantle cell lymphoma. Ibrutinib and palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Palbociclib may also help ibrutinib work better by making cancer cells more sensitive to the drug.

Conditions

Recurrent Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose of the combination of ibrutinib and palbociclib

  Will be defined as the highest dose level at which no more than 1/6 patients present with a dose limiting toxicity (DLT). DLT will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 28 days

Secondary Outcomes (6)

• Overall response rate (ORR)

  Up to 2 years

• Complete response (CR) rate

  Up to 2 years

• Partial response rate

  Up to 2 years

• Progression-free survival (PFS)

  Time from entry onto study until first documentation of objective tumor progression or death due to any cause, whichever occurs first, assessed up to 2 years

• Response duration (RD)

  Time from when criteria for response (CR or partial response [PR]) are met, until first documentation of relapse or progression, assessed up to 2 years

Other Outcomes (1)

• Genetic alterations

  Up to 2 years

Study Arms (1)

Treatment (ibrutinib, palbociclib)

EXPERIMENTAL

Patients receive ibrutinib PO QD on days 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Palbociclib; Other: Pharmacological Study

Interventions

Pharmacological Study OTHER

Correlative studies

Treatment (ibrutinib, palbociclib)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765, Imbruvica, PCI 32765, PCI-32765, PCI32765

Treatment (ibrutinib, palbociclib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib, palbociclib)

Palbociclib DRUG

Given PO

Also known as: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991, PD0332991

Treatment (ibrutinib, palbociclib)

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 histologically or cytologically confirmed mantle cell lymphoma as defined by the World Health Organization; all patients must have either t(11;14) by karyotype or fluorescent in-situ hybridization (FISH) or positive immunohistochemistry for cyclin D1
• Subjects must have measurable disease defined as at least one tumor lesion of at least 1.5 cm or a peripheral blood CD5+, CD19+ lymphocyte count of at least 5,000 cells/uL
• Subjects must have received at least one prior treatment regimen
• Subjects that have received a prior BTK inhibitor or CDK4/6 inhibition are ineligible
• Subjects that have undergone prior allogeneic stem cell transplantation will only be eligible if the transplant occurred at least 1 year prior to study entry, the patient is no longer taking any immunosuppressive therapy, and there are no significant ongoing transplant-related adverse effects
• Subjects must not have received chemotherapy =\< 21 days prior to first administration of study treatment, monoclonal antibody =\< 6 weeks prior to first administration of study treatment, and/or radiotherapy or other investigational agents =\< 4 weeks prior to first administration study treatment unless the subjects' tumor has progressed on the previous therapy and the investigator believes that the patient should not postpone further therapy and, all treatment-related toxicities have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 =\< grade 1; subjects may be receiving equivalent to prednisone at a maximum dose of 20 mg/day orally
• Subjects must be age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Patients must have normal organ and marrow function, independent of transfusion or growth factor support within 14 days before enrollment; patients should not receive growth factors or transfusions for at least 7 days prior to the first dose of study drug, with the exception of pegylated GCSF (pegfilgrastim) and darbepoetin, which require at least 14 days prior to screening and enrollment
• Absolute neutrophil count (ANC) \>= 750 cells/uL (within 14 days before enrollment)
• Platelets \>= 50,000 cells/uL (within 14 days before enrollment)
• Total bilirubin =\< 1.5 times upper limit of normal unless due to Gilbert's disease (within 14 days before enrollment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 times upper limit of normal (within 14 days before enrollment)
• Calculated creatinine clearance \>= 30 mL/min by Cockcroft-Gault (within 14 days before enrollment)
• Corrected QT interval (QTc) =\< 480 ms (within 14 days before enrollment)

You may not qualify if:

• Subjects with known or suspected central nervous system (CNS) involvement are not eligible
• Subjects with serologic status reflecting active viral hepatitis B or C infection are not eligible; subjects that are positive for hepatitis B core antibody positive 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.)
• Subjects with uncontrolled human immunodeficiency virus (HIV) are not eligible; controlled HIV is defined as a CD4 count \> institutional lower limit of normal and no current co-infection; uncontrolled HIV is all other HIV infection; note that patients with controlled infection should be allowed to participate only if they are not receiving prohibited cytochrome P450 (CYP) interactive medications
• Subjects unable to swallow capsules or with disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, resection of the stomach or small bowel, partial or complete bowel obstruction, or symptomatic inflammatory bowel disease are not eligible
• Subjects with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible; recent infections requiring systemic treatment need to have completed therapy \> 14 days before the first dose of the study drugs
• Subjects with uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in declining platelet or hemoglobin levels within the 4 weeks prior to first dose of study drug are not eligible
• Patients with transfusion-dependent thrombocytopenia are not eligible
• Subjects with acute coronary syndrome within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
• Subjects with a history of stroke or intracranial hemorrhage within 6 months prior to enrollment are not eligible
• Subjects with a history of malignancy are not eligible with the exception of the following:
• Malignancy treated within 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
• Female subjects that are pregnant or breastfeeding are not eligible
• Subjects that have received anticoagulation therapy with warfarin or equivalent vitamin K antagonists within the last 28 days are not eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Martin P, Bartlett NL, Blum KA, Park S, Maddocks K, Ruan J, Ridling L, Dittus C, Chen Z, Huang X, Inghirami G, DiLiberto M, Chen-Kiang S, Leonard JP. A phase 1 trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma. Blood. 2019 Mar 14;133(11):1201-1204. doi: 10.1182/blood-2018-11-886457. Epub 2019 Jan 28.

  PMID: 30692121 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; palbociclib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Peter Martin

  Weill Medical College of Cornell University

  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 9, 2014
• First Posted: June 10, 2014
• Study Start: August 13, 2014
• Primary Completion: June 25, 2018
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2025-12

Locations

US (4)