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Recruiting Phase 2

Phase 2 Trial of Lisocabtagene Maraleucel for Minimal Residual Disease in Patients With Large B-cell Lymphoma

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About this study

The goal of the main clinical research study is to learn if treatment with a chimeric antigen receptor (CAR) T-cell therapy called lisocabtagene maraleucel (liso-cel) can help to prevent recurrence of large B-cell cell lymphoma in patients who have achieved complete response (CR) after standard first-line therapy but have tested positive for lymphoma DNA. CAR T therapy is a type of treatment that uses your own immune cells to fight your cancer. The safety of this treatment will also be studied.

Condition
Large B-cell Lymphoma
Tested
Leukapheresis, Lymphodepleting Chemotherapy
Sponsor
M.D. Anderson Cancer Center

Who can join

Age
18 years and older
Sex
All sexes
Healthy volunteers
Not accepted

Inclusion 46

  • Minimum age: 18 years
  • Study condition: Large B-cell Lymphoma
  • Patients must meet the following criteria for study entry:
  • Age ≥18 years 3.
  • Histologically diagnosed 4.
  • Diffuse large B-cell lymphoma, not otherwise specified (NOS) or 5.
  • High grade B-cell lymphoma (NOS or MYC and BCL2 rearrangements) 6.
  • International Prognostic Index score ≥ 3 or 1-2 with LDH \> 1.3 x ULN and/or bulky disease (single lesion of ≥ 7cm) 7.
  • Received first line standard of care anthracycline-based chemoimmunotherapy for 6 cycles (with or without 2 more cycles of rituximab) for previously untreated disease
  • R-CHOP (cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone)
  • DA-EPOCH-R
  • Polatuzumab-R-CHP 8. Achieved complete metabolic response by Lugano criteria4 at the end of treatment response evaluation after first line treatment
  • Or PR only if suitable for observation, defined as either negative biopsy or deemed too small or not amenable to biopsy 9.
  • Had a response assessment within 8 weeks following completion of first line standard of care treatment 10.
  • Detectable MRD after first line treatment (regardless of the ctDNA level) by Foresight CLARITY™12 11.
  • Performance status ≤2 on the ECOG scale (section 6.2.5) 12.
  • Adequate organ and marrow function as defined below:
  • Absolute neutrophil count (ANC) ≥1.0 × 109 /L\*
  • \*Growth factor permitted during screening
  • Platelet count ≥75 × 109 /L
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin ≤ 3 ULN, unless consistent with Gilbert's syndrome
  • AST and ALT ≤ 3x upper limit of normal (ULN)
  • Alkaline phosphatase \< 2.5 ULN
  • Creatinine clearance \>40 ml/min calculated by modified Cockcroft-Gault formula or estimated GFR (eGFR) \> 40 ml/min/1.73m2
  • Cardiac ejection fraction ≥ 40%, no evidence of clinically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings 13. All subjects must
  • Agree to refrain from donating blood while on study treatment, and for at least 12 months following the last dose of study treatment.
  • The effects of liso-cel on the developing human fetus are unknown.
  • For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114).
  • This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
  • Postmenopausal (non-chemically induced menopause in greater than or equal to 12 consecutive months).
  • History of hysterectomy or bilateral salpingo-oophorectomy.
  • Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
  • History of bilateral tubal ligation or another surgical sterilization procedure.
  • \. Females of childbearing potential (FCBP) must:
  • Have 2 negative pregnancy tests as verified by the Investigator (one negative serum beta-human chorionic gonadotropin \[ß-hCG\] pregnancy test result at screening, and within 7 days prior to the first dose of LD chemotherapy). This applies even if the subject practices true abstinence2 from heterosexual contact.
  • Either commit to true abstinence from heterosexual contact (which must be reviewed monthly and source documented) or agree to use, and be able to comply with, effective contraception without interruption.
  • Contraception methods must include 1 highly effective method from screening until at least 12 months after the LD chemotherapy.
  • Agree to abstain from breastfeeding during study participation and for at least 12 months following LD chemotherapy.
  • Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide.
  • Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.
  • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • \. Male subjects must:
  • Male Practice true abstinence (which must be reviewed monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for 12 months after LD chemotherapy even if he has undergone a successful vasectomy.
  • \. Willing and able to comply with the protocol treatment and procedures. 18. Ability to understand and the willingness to sign a written informed consent document.

Exclusion 39

  • Subjects will be ineligible for this study if they meet any of following criteria:
  • Having radiologically confirmed relapsed/refractory disease.
  • Have not recovered from non-hematological AEs due to prior first line therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
  • Known central nervous system lymphoma or leptomeningeal disease.
  • Suspicious case at end of treatment from first line treatment should be evaluated with brain MRI with or without lumber puncture.
  • Any prior history of other malignancy besides B-NHL, unless the patient has been free of disease for ≥ 2 years and felt to be at low risk for recurrence by the treating physician, except:
  • Adequately treated localized non-melanoma skin cancer without evidence of disease.
  • Adequately treated localized prostate cancer without evidence of disease.
  • Adequately treated localized breast cancer without evidence of disease.
  • Adequately treated cervical carcinoma in situ without evidence of disease.
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at undue risk.
  • Uncontrolled human immunodeficiency virus (HIV), or active Hepatitis C Virus, or active Hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed JC virus infection and SARS-CoV2.
  • Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated.
  • The treatment and monitoring of hepatitis B will follow the institutional standard of practice.
  • Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR).
  • Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded.
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result.
  • Those who are hepatitis C PCR positive will be excluded.
  • Subjects with a history of Hepatitis C who received antiviral treatment are eligible as long as PCR is negative.
  • History of severe allergic or anaphylactic reactions or intolerance to anti-CD20 monoclonal antibody therapy or any bispecific antibody.
  • History of immunodeficiency (with the exception of hypogammaglobulinemia) or concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of \>10mg/day of prednisone) within 28 days of the first dose of study drug with exception of steroid used for IV contrast allergy.
  • In addition, use of inhaled, topical, intranasal corticosteroids or local steroid injection (eg, intra- articular injection) is permitted.
  • Clinically significant cardiovascular diseases such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification.
  • Subjects with controlled, asymptomatic heart failure during screening can enroll on study.
  • History or presence of clinically significant central nervous system (CNS) pathology such as epilepsy (a seizure disorder), a seizure within the past 2 years prior to signing the ICF, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, Grade 3 or higher tremor, cerebellar disease, organic brain syndrome, or psychosis.
  • Lactating or pregnant subjects.
  • Pregnant women are excluded from this study for unknown potential for teratogenic or abortifacient effects by liso-cel.
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with liso-cel, breastfeeding should be discontinued if the mother is treated with liso-cel.
  • These potential risks may also apply to other agents used in this study.
  • Had blood transfusion within 14 days prior to first dose of LDC.
  • Administration of any investigational agent within 28 days of first dose of study drug.
  • Patients who have undergone major surgery within 28 days or minor surgery within 3 days of first dose of study drug.
  • Administration of a live, attenuated vaccine within 4 weeks before lymphodepleting treatment administration or anticipation that such a live, attenuated vaccine will be required during the study.
  • Patients taking chronic corticosteroids for other diseases, unless administered at a dose equivalent to \< 10 mg/day prednisone.
  • For corticosteroids, prednisolone \>20 mg daily (or equivalent) qualifies as immunosuppressive and thus is excluded for this use.
  • Note: corticosteroids at any dose are permitted for control of lymphoma-related symptoms, including during screening, and for prophylaxis or AE management during the trial.
  • Patients who have concern for the accurate assessment of neuro toxicity.
  • Patients who have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  • Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.

Where

1 site, 1 recruiting

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States

Recruiting

Contact

Potential match only. Final eligibility is determined by the study team.