Phase II Palbociclib +Ibrutinib in Mantle Cell Lymphoma

NCT03478514 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AFT-32
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 9

Brief Summary

The proposed study is a single-arm, multi-center, open-label phase II study of the combination of palbociclib and ibrutinib in patients with previously treated mantle cell lymphoma to evaluate the efficacy of this combination, with the primary objective of the study being to assess median PFS and the secondary objectives to include ORR, CR, DOR, OS and toxicity. Subjects will be enrolled and treated with palbociclib and ibrutinib with each cycle of therapy being 28 days. Treatment will be based on the recommended phase II dose (RP2D) from the phase I combination trial.

Conditions

B Cell Lymphoma; Mantle Cell Lymphoma

Keywords

mantle cell lymphoma; B-cell lymphoma; palbociclib

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Time interval between registration and progression or death

  42 months

Secondary Outcomes (5)

• Overall survival

  42 months

• Duration of response

  42 months

• Overall Response Rate

  42 Months

• Complete Response

  42 Months

• Toxicity: Incidence and severity of adverse events by summaries of toxicity data/contingency tables

  42 Months

Study Arms (1)

Single Arm

EXPERIMENTAL

All patients will receive palbociclib at 100 mg oral once a day for 21 days, followed by 7 days off. Ibrutinib will be administered at 560 mg oral continuously.

Drug: Palbociclib; Drug: Ibrutinib

Interventions

Palbociclib DRUG

Taken at 100 mg once daily for 21 days, followed by 7 days off

Also known as: Ibrance; PD-0332991

Single Arm

Ibrutinib DRUG

560 mg taken orally all patients throughout the study

Also known as: Imbruvica

Single Arm

Eligibility Criteria

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

You may qualify if:

• Subjects must have histologically or cytologically confirmed MCL 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 (IHC) for cyclin D1.
• Subjects must have measurable disease defined as at least one tumor lesion of at least 1.5 cm by CT or MRI, PET positive lesion(s) or a peripheral blood CD5+, CD19+ lymphocyte count of at least 5,000 cells/µL.
• Subjects must have received at least one prior systemic therapy.
• Subjects who have received prior autologous stem cell transplant are eligible. Patients that have undergone prior allogeneic stem cell transplant will only be eligible if the patient is no longer taking immunosuppressive therapy and there are no significant ongoing transplant-related adverse effects.
• Subjects must be age ≥ 18 years
• ECOG performance status ≤ 2
• Patients must have normal organ and marrow function as defined below:
• Laboratory Values:
• ANC ≥ 1000 cells/μL, unless bone marrow involvement in MCL, then ANC \>500 cells/μL;
• Platelets ≥ 75,000 cells/μL, unless bone marrow involvement in MCL, then platelets \>30,000 cells/μL;
• Calculated creatinine clearance ≥30mL/min;
• AST or ALT ≤ 2.5x ULN;
• Total bilirubin ≤ 1.5x ULN;
• QTc ≤ 480 ms
• Subjects must be able to provide written, informed consent

You may not qualify if:

• Subjects that have received prior CDK4/6 inhibitor will not be eligible.
• Subjects that have received any prior BTK inhibitor \> 90 days prior to enrollment will not be eligible.
• Subjects with known or suspected CNS involvement.
• Concurrent therapy with other investigational products.
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
• Subjects receiving any medications or substances that are strong or moderate inhibitors or strong inducers of CYP3A isoenzymes within 7 days of starting study treatment (See Appendix II).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects with myocardial infarction 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 ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to registration, irrespective of the method of contraception used, are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Breastfeeding should be discontinued prior to study entry.
• Subjects must agree to use barrier contraceptive methods throughout the study period up until at least 90 days post last palbociclib dose.
• Subjects with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis, etc.
• Subjects with another active malignancy that limits survival.
• Subjects with a bleeding diathesis are not eligible.
• Subjects with transfusion-dependent thrombocytopenia are not eligible.

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Pfizer: collaborator

Study Sites (9)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

St. Joseph Mercy Hospital Cancer Care Center

Ypsilanti, Michigan, 48197, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina - Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Related Publications (8)

• Herrmann A, Hoster E, Zwingers T, Brittinger G, Engelhard M, Meusers P, Reiser M, Forstpointner R, Metzner B, Peter N, Wormann B, Trumper L, Pfreundschuh M, Einsele H, Hiddemann W, Unterhalt M, Dreyling M. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol. 2009 Feb 1;27(4):511-8. doi: 10.1200/JCO.2008.16.8435. Epub 2008 Dec 15.

  PMID: 19075279 BACKGROUND

• Medema RH, Herrera RE, Lam F, Weinberg RA. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6289-93. doi: 10.1073/pnas.92.14.6289.

  PMID: 7603984 BACKGROUND

• Fry DW, Bedford DC, Harvey PH, Fritsch A, Keller PR, Wu Z, Dobrusin E, Leopold WR, Fattaey A, Garrett MD. Cell cycle and biochemical effects of PD 0183812. A potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. J Biol Chem. 2001 May 18;276(20):16617-23. doi: 10.1074/jbc.M008867200. Epub 2001 Feb 6.

  PMID: 11278443 BACKGROUND

• Marzec M, Kasprzycka M, Lai R, Gladden AB, Wlodarski P, Tomczak E, Nowell P, Deprimo SE, Sadis S, Eck S, Schuster SJ, Diehl JA, Wasik MA. Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity. Blood. 2006 Sep 1;108(5):1744-50. doi: 10.1182/blood-2006-04-016634. Epub 2006 May 11.

  PMID: 16690963 BACKGROUND

• Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19.

  PMID: 23782157 BACKGROUND

• 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 BACKGROUND

• Chiron D, Di Liberto M, Martin P, Huang X, Sharman J, Blecua P, Mathew S, Vijay P, Eng K, Ali S, Johnson A, Chang B, Ely S, Elemento O, Mason CE, Leonard JP, Chen-Kiang S. Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov. 2014 Sep;4(9):1022-35. doi: 10.1158/2159-8290.CD-14-0098. Epub 2014 Jul 31.

  PMID: 25082755 BACKGROUND

• Leonard JP, LaCasce AS, Smith MR, Noy A, Chirieac LR, Rodig SJ, Yu JQ, Vallabhajosula S, Schoder H, English P, Neuberg DS, Martin P, Millenson MM, Ely SA, Courtney R, Shaik N, Wilner KD, Randolph S, Van den Abbeele AD, Chen-Kiang SY, Yap JT, Shapiro GI. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood. 2012 May 17;119(20):4597-607. doi: 10.1182/blood-2011-10-388298. Epub 2012 Mar 1.

  PMID: 22383795 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, B-Cell

Interventions

palbociclib; ibrutinib

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

• Evanthia Galanis, MD

  Alliance Foundation Trials, LLC.

  PRINCIPAL INVESTIGATOR

• Kami Maddocks, MD

  Ohio State University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The proposed study is a single-arm, multi-center, open-label phase II study of the combination of palbociclib and ibrutinib in patients with previously treated mantle cell lymphoma.

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: March 27, 2018
• Study Start: September 11, 2018
• Primary Completion: November 10, 2025
• Study Completion (Estimated): August 30, 2026
• Last Updated: April 9, 2026

Record last verified: 2025-09

Locations

US (9)