Non Hodgkin Lymphoma Clinical Trial

Pemigatinib for the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma or Marginal Zone Lymphoma

Summary

This phase II trial tests how well pemigatinib works in treating patients with mantle cell lymphoma (MCL) or marginal zone lymphoma (MZL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Pemigatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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Full Description

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of pemigatinib in patients with relapsed or refractory (R/R) MCL.

II. To evaluate the efficacy of pemigatinib in patients with R/R MZL.

SECONDARY OBJECTIVES:

I. To evaluate the complete response (CR) rate at end of cycle 6 (C6). II. To evaluate the duration of response (DOR). III. To evaluate the median and 2-year progression-free survival (PFS). IV. To evaluate the median and 2-year overall survival (OS).

EXPLORATORY OBJECTIVE:

I. To evaluate the factors predictive of response to pemigatinib and identify mechanism of resistance to therapy.

OUTLINE:

Patients receive pemigatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also under computed tomography (CT) and positron emission tomography (PET) or PET/CT and blood sample collection at screening and on study. Patients may also undergo bone marrow aspirate and biopsy during screening and on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 or 6 months.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

Histologically documented MCL or MZL, including extranodal marginal zone lymphoma (EMZL)/mucosa-associated lymphoid tissue (MALT) lymphoma, splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL)

Patients with gastric MALT lymphoma and those who are Helicobacter (H.) pylori positive need to have failed a trial of H. pylori eradication and are either ineligible, refused, or failed gastric radiation therapy
At least two prior lines of systemic therapy and patients do not have Food and Drug Administration (FDA) approved available therapies or refuse them

Prior autologous hematopoietic cell transplantation (auto-HCT) and chimeric antigen receptor (CAR)-T cell therapy are eligible.

Patients with prior auto-HCT may be eligible if treatment completed after at least 3 months prior to first treatment
Patients with CAR T-cell therapy may be eligible if treatment completed after at least 1 month prior to first treatment
Patients must have an indication for systemic treatment
Radiographically measurable disease by computed tomography (CT) scan, defined as at least one lesion > 1.5 cm in size or assessable disease in the opinion of the investigator
Life expectancy of > 3 months, in the opinion of the investigator

Willingness to avoid pregnancy or fathering children based on the criteria below:

Woman of nonchildbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea)
A woman of childbearing potential who has a negative pregnancy test at screening and before the first dose on day 1 and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed. A follow-up pregnancy test will be performed at end of treatment (EOT) visit
Men who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after last day of treatment (1 sperm cycle). Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed
Absolute neutrophil count (ANC) ≥ 1000 cells/mm^3 (≥ 1.0 x 10^9/L) independent of granulocyte colony stimulating factor (G-CSF) support (i.e., no G-CSF within the past 3 days), unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case ANC of 750 cells/mm^3 (0.75 x 10^9/L) is permissible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow
Platelet count ≥ 75,000 cells/mm^3 (≥ 75 x 10^9/L) independent of transfusion support (i.e., no transfusion within the past 3 days) unless there is documented bone marrow involvement in which case platelet count of 50,000 cells/mm^3 (0.5 x 10^9/L) is permissible. Patients must be responsive to transfusion support if given for thrombocytopenia and patients refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow
Hemoglobin of ≥ 8 g/dL (≥ 80 g/L) independent of transfusion support (i.e., no transfusion within the past 3 days) unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case hemoglobin of 7 g/dL (70 g/L) is permissible. Patients must be responsive to transfusion support if given for anemia and patients refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow
Total bilirubin < 1.5 x upper limit of normal (ULN) or < 2.5 x ULN with document liver involvement and/ or Gilbert's disease
Transaminases (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) ≤ 2.5 x ULN or ≤ 5 x ULN with documented liver involvement
Calculated creatinine clearance > 30 mL/min according to Cockcroft/Gault Formula
Ability to swallow oral tablets
Patients or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial
Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol

Exclusion Criteria:

Prior receipt of FGFR inhibitor
Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug
Major surgery within 4 weeks prior to enrollment
Received prior radiation therapy administered within 4 weeks of first dose of study drug. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have radiation pneumonitis. A 2-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease
A 4 week wash out from the prior cytotoxic chemotherapy, a 3 week wash out from prior monoclonal antibody and a 2 week wash out from prior BTK inhibitor. The wash out interval is based on the last day of the prior therapy to the start of the study drug (cycle 1 day 1 [C1D1])
Concurrent anticancer therapy except as listed for prostate and breast cancer

Significant cardiovascular disease defined as:

Unstable angina or acute coronary syndrome within the past 2 months prior to study enrollment
History of myocardial infarction within 3 months prior to study enrollment or
Documented left ventricular ejection fraction (LVEF) by any method of ≤ 40% in the 12 months prior to study enrollment
≥ grade 3 New York Heart Association (NYHA) functional classification system of heart failure, uncontrolled or symptomatic arrhythmias
Patients with CNS involvement

Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia's Formula (QTcF)

Correction of suspected drug induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation

Correction for underlying bundle branch block (BBB) allowed

Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
Patients who have tested positive for human immunodeficiency virus (HIV). For patients with unknown HIV status, HIV testing will be performed at screening and result should be negative for enrollment

Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:

Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are HBV deoxyribonucleic acid (DNA) PCR positive will be excluded. Patients with positive anti-HBc and negative HBV DNA should be on prophylactic nucleo(t)side analogue therapy to prevent reactivation with serial HBV DNA PCR monitoring
Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before enrollment. Patients who are hepatitis C RNA positive will be excluded. Patients with SMZL who have chronic HCV will need to have undergone antiviral treatment to participate
Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal, or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and medical monitor may pose a risk for patient participation. Screening for chronic conditions is not required
Active second malignancy unless in remission and with life expectancy > 2 years
Are pregnant and breast feeding
Pregnancy or nursing women or subjects expecting to conceive or father children within the projected duration of the study, starting with the screening visit through completion of safety follow-up visit (90 days from date of last dose for male subjects)
History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification
Current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic examination
Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Moderate CYP3A4 inhibitors are not prohibited but should be avoided
Subject with history of hypovitaminosis D requiring supraphysiologic dose (such as 50,000 IU of vitamin D3) to replenish the deficiency. Subjects receiving vitamin D food supplements are allowed
Have a known hypersensitivity to any of the excipients of pemigatinib
Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination
Patients with ongoing grade ≥ 2 toxicity from prior therapy, with exceptions such as alopecia

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

25

Study ID:

NCT06300528

Recruitment Status:

Not yet recruiting

Sponsor:

Narendranath Epperla

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There is 1 Location for this study

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Ohio State University Comprehensive Cancer Center
Columbus Ohio, 43210, United States More Info
Narendranath Epperla, MD, MS
Contact
614-393-3196
Narendranath Epperla, MD, MS
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

25

Study ID:

NCT06300528

Recruitment Status:

Not yet recruiting

Sponsor:


Narendranath Epperla

How clear is this clinincal trial information?

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