Phase II Palbociclib +Ibrutinib in Mantle Cell Lymphoma

  • STATUS
    Recruiting
  • End date
    Dec 30, 2022
  • participants needed
    61
  • sponsor
    Alliance Foundation Trials, LLC.
Updated on 30 July 2021
rituximab
prednisone
immunosuppressive agents
measurable disease
lamivudine
hepatitis b surface antigen
immunohistochemistry
mantle cell lymphoma
ibrutinib
btk inhibitor
hepatitis b core antibody
cyclin d1

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.

Description

Treatment will consist of:

  • Palbociclib administered at 100 mg oral once daily for 21 days on followed by 7 days off
  • Ibrutinib administered at 560 mg oral continuously

Patients will continue to receive study drugs until disease progression, unacceptable toxicity, or withdrawal of consent. If at any time one of the agents is held due to toxicity, the other agent may be continued in those patients who are receiving clinical benefit.

Response will be assessed by PET/CT and/or CT every 3 cycles while on therapy for the first year and then every 6 cycles thereafter until disease progression or at the investigator's discretion if otherwise medically indicated. A PET will be required to confirm CR. A bone marrow biopsy will be performed in patients with bone marrow involvement at the start of therapy to confirm complete response once patients have otherwise met criteria for CR.

Details
Condition Lymphoma, Mantle cell lymphoma, B-Cell Lymphoma, Non-Hodgkin's Lymphoma, Lymphoma, B-Cell, b-cell lymphomas, b cell lymphomas, b cell lymphoma
Treatment Ibrutinib, Palbociclib
Clinical Study IdentifierNCT03478514
SponsorAlliance Foundation Trials, LLC.
Last Modified on30 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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/L
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
Subjects that have received either prior BTK inhibitor or CDK4/6 inhibitor will not be eligible
Patients must have normal organ and marrow function as defined below
Laboratory Values
ANC 1000 cells/L
Platelets 75,000 cells/L
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
Subjects must have recovered from adverse events to grade 1 from prior therapies
Subjects must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption
Subjects may be receiving prednisone at a maximum dose of 20 mg orally daily for symptom control
Serum or urine pregnancy test must be negative within 7 days of starting study treatment in women of childbearing potential. Women of childbearing potential and men with female partners who are able to become pregnant are required to use a highly effective form of barrier contraception for the duration of the study and for 90 days after the last dose of study drug. Adequate contraception is defined as abstinence or two forms non hormonal contraception, which is a combination of two forms of the
following
Condom with spermicidal foam/gel/cream/suppository
occlusive cap (diaphragm or cervical vault caps) with spermicidal
non hormonal intrauterine device (IVD)
No evidence of active hepatitis B or C infections (i.e., no positive serology for anti-HBc or anti-HCV antibodies)
HBV seropositive patients (HBsAg +) are eligible if they are closely monitored for evidence of active HBV infection by HBV DNA testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose
Patients with HIV infection are eligible, provided they meet the following
No evidence of coinfection with hepatitis B or C
CD4+ cell count 400/mm3
No evidence of resistant strains of HIV
If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL
No history of AIDS-defining conditions
No use of strong CYP3A4/5 inhibitors or inducers

Exclusion Criteria

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
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