A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies (COBALT-LYM)

Overview

About this study

The primary objectives of this study are:

Part A (Dose escalation):

  • To assess the safety of escalating doses and/or dosing regimens of CTX130 in subjects with relapsed/refractory T or B cell malignancies and to determine one or more recommended Part B dose (RPBD) regimens

Part B (Cohort expansion):

  • To assess the efficacy of CTX130 as measured by objective response rate (ORR) in the following 2 expansion arms, according to Lugano response criteria (Cheson et al., 2014) or International Society for Cutaneous Lymphomas (ISCL) response criteria (Olsen et al., 2011)

− MF/SS (advanced and transformed)

− PTCL

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

1.  ≥18 years of age

2. Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document

3. For subjects with T cell lymphoma, only the following subtypes will be enrolled:

• PTCL-NOS

• ALCL

• SS or MF ≥Stage IIB with ≥2-compartment disease or single compartment disease with large cell transformation

• Leukemic and lymphomatous subtypes of ATLL

• AITL

• Subjects with PTCL-NOS, leukemic and lymphomatous ATLL, or AITL should have failed ≥1 lines of systemic therapy.

• Subjects with ALCL should have failed, be ineligible for, or have refused combination chemotherapy and therapy with brentuximab vedotin in combination or as single agent.

− Subjects with ALK− ALCL should have failed a minimum of 1 prior line of therapy

− Subjects with ALK+ ALCL should have failed a minimum of 2 prior lines of therapy

• Subjects with MF or SS must have failed at least 2 of the following systemic or total body directed therapies: brentuximab vedotin, romidepsin (or other indicated histone deacetylase inhibitors), pralatrexate, mogamulizumab, total skin electron beam therapy (TSEBT), pembrolizumab, or other systemic chemotherapy. If mogamulizumab was the last therapy prior to enrollment, there must be at least 50 days between the last dose of mogamulizumab and the infusion of CTX130.

4. For subjects with B cell lymphoma:

• DLBCL in subjects who have received up to 4 lines of prior systemic therapy, including autologous CD19-directed CAR T cell therapy unless autologous CD19-directed CAR T cell therapy was refused or attempted and failed manufacturing

5. Subjects must have CD70-expressing tumors as determined by laboratories meeting applicable local requirements (e.g., Clinical Laboratory Improvement Amendments or equivalent for non-US locations) by either:

• CD70 positivity (≥10% of cells) by IHC in tissue collected by excisional or core biopsy of a representative tumor lesion. In cases where more than one sample is submitted, a single sample testing positive will be sufficient for eligibility.

• CD70 positivity (≥10% of cells) by flow cytometry in tumor cells defined by immunophenotyping collected in the peripheral blood or bone marrow at screening

6. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion at screening unless a biopsy performed within 3 months prior to enrollment and after the last systemic or targeted therapy post progression is available

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Appendix C)

8. Meets protocol-specified criteria to undergo daratumamab infusion (Parts A2, A4, and A6 only), LD chemotherapy, and CAR T cell infusion

9. Adequate organ function:

• Renal: creatinine clearance (CrCl) ≥50 mL/min

• Liver:

− Aspartate aminotransferase and alanine aminotransferase <3 × upper limit of normal (ULN)

− Total bilirubin <2 × ULN (for Gilbert’s syndrome: total bilirubin <3 mg/dL and normal conjugated bilirubin)

• Cardiac: Hemodynamically stable and left ventricular ejection fraction (LVEF) ≥45% by echocardiogram

• Pulmonary: Oxygen saturation level on room air >92% per pulse oximetry

• Hematologic: Platelet count >25,000/mm3 and absolute neutrophil count >500/mm3

10. Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least 1 ovary, and is less than 1 year postmenopausal) must agree to use a highly effective method of contraception (as specified in Appendix D) from enrollment through at least 12 months after last CTX130 infusion

11. Male subjects must agree to use acceptable effective method(s) of contraception (as specified in Appendix D) from enrollment through at least 12 months after last CTX130 infusion

12. Subjects must have measurable disease per mSWAT or peripheral blood tumor burden, or at least 1 measurable lesion by imaging (PET-CT or CT) according to Lugano criteria; lesion cannot have been biopsied or irradiated

Exclusion Criteria:

1. Prior allogeneic SCT

2. Less than 60 days from autologous SCT at time of screening and with unresolved serious complications

3. Prior treatment with anti-CD70 targeting agents

4. For subjects with DLBCL, prior treatment with CAR T cells or other modified T or NK cells except autologous CD19-directed CAR T cells

5. Known contraindication to daratumumab (Parts A2, A4, and A6 only), any LD chemotherapy agent(s), or any of the excipients of CTX130 product

6. T cell or B cell lymphomas with a present or past malignant effusion that is or was symptomatic

7. Clinical signs of HLH: A combination of fever, bicytopenia, hypertriglyceridemia or hypofibrinogenemia and ferritin >500 μg/L

8. Active central nervous system (CNS) manifestation of underlying disease in screening imaging (i.e., brain MRI)

9. History or presence of clinically relevant CNS pathology such as seizure, stroke, severe brain injury, cerebellar disease, myelopathy (e.g., tropical spastic paraparesis), history of posterior reversible encephalopathy syndrome with prior therapy, or another condition that in opinion of investigator may increase CAR T-related toxicities

10. Unstable angina, arrhythmia, or myocardial infarction within 6 months prior to screening

11. Ongoing bacterial, viral, or fungal infection requiring systemic anti-infectives

12. Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), or active hepatitis B virus or hepatitis C virus infection. Subjects with prior history of hepatitis B or C infection who have documented undetectable viral load (by quantitative polymerase chain reaction [PCR] or nucleic acid testing) are permitted.

13. Previous or concurrent malignancy, except for the following:

• Those treated with curative approach who have been in remission for >12 months without requiring systemic therapy (antihormonal therapy accepted)

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.

• Adequately treated cervical carcinoma in situ without evidence of disease.

• Adequately treated breast ductal carcinoma in situ without evidence of disease.

• Prostatic intraepithelial neoplasia without evidence of prostate cancer.

• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ

14. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy

15. Prior solid organ transplantation

16. Prior use of antitumor agents, except palliative radiotherapy in consultation with medical monitor, 14 days prior to LD chemotherapy. For investigational agents, washout time needs to be discussed with the medical monitor. Use of physiological doses of steroids (≤10 mg/day of prednisone or equivalent doses of other corticosteroids) will be permitted for subjects previously on steroids. Intrathecal prophylaxis for subjects with ATLL is permitted if indicated per investigator assessment. Subjects with ATLL receiving the receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor denosumab should be on therapy for at least 4 weeks and must have stabilized corrected serum calcium levels; and are excluded if serum calcium level is >11.5 mg/dL or >2.9 mmol/L, or ionized calcium level is >1.5 mmol/L. Use of CCR-4–directed antibodies is prohibited 3 months prior to CTX130 infusion, except for mogamulizumab, which is prohibited 50 days prior to CTX130 infusion.

17. Diagnosis of significant psychiatric disorder that could seriously impede the subject’s ability to participate in the study

18. Received live vaccines or herbal medicines as part of traditional Chinese medicine or non-over-the-counter herbal remedies within 28 days prior to enrollment

19. Pregnant or breastfeeding females

 

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Jose Villasboas Bisneto, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Hemant Murthy, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Javier Munoz, M.D., M.B.A.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20531308

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