RECRUITING

Safety and Preliminary Efficacy of MT-601 in Patients With Relapsed/Refractory Lymphoma

Conditions

Non-Hodgkin Lymphoma, Adult Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, Relapsed Non Hodgkin Lymphoma Hodgkin Lymphoma Hodgkin Lymphoma, Adult Hodgkin's Lymphoma, Relapsed, Adult NHL Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is a Phase 1 multicenter study with a Dose Escalation and Dose Expansion evaluating safety and efficacy of MT-601 administration to patients with Relapsed or Refractory Lymphoma. The starting dose administered is 200 x 10\^6 cells (flat dosing).

Official Title

A Phase 1 Study of Patient-Derived Multi-Tumor-Associated Antigen-Specific T Cells (MT-601) Administered to Patients With Relapsed or Refractory Non-Hodgkin and Hodgkin Lymphoma (APOLLO)

Quick Facts

Study Start:2023-01-02

Study Completion:2028-02-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05798897

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 100 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* All applicable inclusion and exclusion criteria must be met at Screening and at Baseline (re-assessment of eligibility within 14 days prior to group assignment). 1. Participant must be ≥ 18 years of age and capable of giving signed informed consent (ICF), which includes compliance with the requirements and restrictions listed in the ICF and in the protocol, at the time of signing the ICF. 2. Cytologically or histologically confirmed diagnosis of NHL, HL or CLL based on the 2022 World Health Organization (WHO) criteria for hematolymphoid neoplasms 3. Enrollment of the following subtypes will be eligible: 1. LBCL including diffuse large B cell lymphoma, primary mediastinal B cell lymphoma (PMBCL), high grade B cell lymphoma (HGBL), T cell rich B cell lymphoma and transformed indolent lymphoma (transformed iNHL) 2. FL 3. MCL 4. MZL 5. HL 6. CLL/SLL 7. CNS lymphoma 8. CAR T cell refractory 4. Must have measurable disease as per 2014 Lugano criteria or 2018 iwCLL criteria. Participants with splenic MZL must have measurable splenomegaly on imaging or evidence of bone marrow involvement. 5. Participants who are R/R, are intolerant to, or are considered ineligible for systemic standard of care anticancer treatments, including at least 2 prior therapies. Participants who refuse standard of care treatments may also be considered if documentation is provided that he/she has been made aware of all therapeutic options. 6. For participants with LBCL, FL, and MCL: Have received CD19-directed CAR T cell therapy and relapsed ≥ 30 days or attained an incomplete response as the best response within 1 year after CAR T cell administration. Participants who refuse or are ineligible for CAR T cell therapy are eligible for this study. Note: during Dose Expansion, a specific cohort may be enrolled to evaluate participants who were refractory to CD19-directed CAR T cell therapy. 7. Karnofsky score of ≥70 or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale 8. Life expectancy ≥12 weeks 9. Adequate blood, liver, renal and cardiac function: 1. Hematology: Hemoglobin ≥ 7.0 g/dL (can be transfused), absolute lymphocyte count (ALC) ≥ 300/μL, (prior to apheresis only), absolute neutrophil count (ANC) ≥ 750/μL and platelet count ≥ 50,000/μL (prior to the conditioning regimen only) 2. Liver: Bilirubin ≤ 1.5X upper limit of normal (ULN) (exception of bilirubin elevation due to Gilbert's syndrome 3X); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3X ULN 3. Renal: Serum creatinine ≤ 1.5X ULN or measured or calculated creatinine clearance ≥ 50 mL/min (prior to the conditioning regimen) 4. Cardiac: left ventricular ejection fraction ≥ 45% (prior to the leukapheresis) Sex 10. Female: Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (i.e., with a failure rate of \< 1% per year), preferably with low user dependency during the intervention period and for at least 6 months after the last infusion of MT-601 and agrees not to donate eggs (i.e., ova and oocytes) for the purpose of reproduction during this period 11. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 6 months after the last infusion of MT-601:	* Patients are excluded from the study if any of the following criteria apply: 1. Evidence of bulky disease at the time of the conditioning regimen (≥ 10 cm in diameter for LBCL or HL and \> 6 cm for other subtypes) 2. Untreated or ongoing treatment for CNS lymphoma or completed treatment within 2 weeks of apheresis (Note: May be allowed in Dose Expansion if disease specific cohort for CNS lymphoma is opened) 3. Refractory to CAR T therapy defined as a best response of stable disease or disease progression (Note: May be allowed in Dose Expansion if disease specific cohort for CAR T cell therapy refractory is opened) 4. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression Medical Conditions 5. Primary immunodeficiency 6. Severe or uncontrolled autoimmune disorder 7. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis 8. Unresolved immune effector cell-associated neurotoxicity syndrome (ICANS) from prior CAR T cell administration. Consideration for Grade 1 may be made after discussion with the Medical Monitor 9. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast, and/or prostate) unless disease free for at least 3 years 10. Cardiac conditions: 1. Medically uncontrolled hypertension (≥ 160 mmHg systolic blood pressure or ≥ 100 mmHg diastolic blood pressure) 2. Congestive heart failure Class ≥ II as defined by the New York Heart Association 3. Acute coronary syndrome (including unstable angina, coronary artery stenting, or angioplasty, bypass grafting within prior 6 months) 4. History or evidence of current, uncontrolled, clinically significant, unstable arrhythmias 11. Oxygen saturation at room air \< 92% 12. Participant has known human immunodeficiency virus (HIV) infection, or active hepatitis B virus (HBV)/hepatitis C virus (HCV) infection 13. Acute bacterial, viral, fungal infection requiring systemic therapy (uncomplicated urinary tract infection and bacterial pharyngitis are permitted if responding to therapy) 14. History of severe allergic reactions to any of the study intervention components including conditioning regimen, dimethyl sulfoxide (DMSO) or to tocilizumab 15. Clinically significant reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline * Participants with Grade 2 neuropathies due to prior treatment will be allowed on study. * Participants with clinical nonsignificant toxicities, such as alopecia, will be allowed on study. 16. Receipt of allogeneic hematopoietic cell transplant (HCT) within 12 months; on immunosuppression or with evidence of donor/mixed chimera 17. Receipt of autologous HCT within 3 months 18. Treatment with CD19-directed CAR T cell therapy within 3 months 19. Treatment with bispecific antibody within 1 month 20. Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days 21. Treatment with monoclonal antibodies impacting T cell function within 14 days 22. Treatment with systemic immunosuppression including systemic corticosteroids (unless ≤5 mg/day oral prednisone or steroid equivalent) within 14 days 23. Treatment with chemotherapy within 7 days 24. Treatment with a live, attenuated vaccine within 4 weeks 25. Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days 26. Treatment with chemotherapy or biologics/monoclonal antibodies within 14 days 27. Treatment with radiation therapy within 7 days 28. Treatment with a tyrosine kinase inhibitor (TKI) within 7 days or 5 half-lives (whichever is longer) before conditioning regimen 29. Hematopoietic growth factors \<2 days 30. Treatment with experimental CAR T cell product unless approved by Medical Monitor 31. Treatment with other cancer therapy including investigational agents that do not fit in the above categories within 14 days 32. Major surgery within 14 days 33. Pregnant or lactating 34. Any other issue which, in the opinion of the treating physician, would make the participant ineligible for the study

Inclusion Criteria

Exclusion Criteria

* All applicable inclusion and exclusion criteria must be met at Screening and at Baseline (re-assessment of eligibility within 14 days prior to group assignment).
1. Participant must be ≥ 18 years of age and capable of giving signed informed consent (ICF), which includes compliance with the requirements and restrictions listed in the ICF and in the protocol, at the time of signing the ICF.
2. Cytologically or histologically confirmed diagnosis of NHL, HL or CLL based on the 2022 World Health Organization (WHO) criteria for hematolymphoid neoplasms
3. Enrollment of the following subtypes will be eligible:
1. LBCL including diffuse large B cell lymphoma, primary mediastinal B cell lymphoma (PMBCL), high grade B cell lymphoma (HGBL), T cell rich B cell lymphoma and transformed indolent lymphoma (transformed iNHL)
2. FL
3. MCL
4. MZL
5. HL
6. CLL/SLL
7. CNS lymphoma
8. CAR T cell refractory
4. Must have measurable disease as per 2014 Lugano criteria or 2018 iwCLL criteria. Participants with splenic MZL must have measurable splenomegaly on imaging or evidence of bone marrow involvement.
5. Participants who are R/R, are intolerant to, or are considered ineligible for systemic standard of care anticancer treatments, including at least 2 prior therapies. Participants who refuse standard of care treatments may also be considered if documentation is provided that he/she has been made aware of all therapeutic options.
6. For participants with LBCL, FL, and MCL: Have received CD19-directed CAR T cell therapy and relapsed ≥ 30 days or attained an incomplete response as the best response within 1 year after CAR T cell administration. Participants who refuse or are ineligible for CAR T cell therapy are eligible for this study. Note: during Dose Expansion, a specific cohort may be enrolled to evaluate participants who were refractory to CD19-directed CAR T cell therapy.
7. Karnofsky score of ≥70 or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
8. Life expectancy ≥12 weeks
9. Adequate blood, liver, renal and cardiac function:
1. Hematology: Hemoglobin ≥ 7.0 g/dL (can be transfused), absolute lymphocyte count (ALC) ≥ 300/μL, (prior to apheresis only), absolute neutrophil count (ANC) ≥ 750/μL and platelet count ≥ 50,000/μL (prior to the conditioning regimen only)
2. Liver: Bilirubin ≤ 1.5X upper limit of normal (ULN) (exception of bilirubin elevation due to Gilbert's syndrome 3X); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3X ULN
3. Renal: Serum creatinine ≤ 1.5X ULN or measured or calculated creatinine clearance ≥ 50 mL/min (prior to the conditioning regimen)
4. Cardiac: left ventricular ejection fraction ≥ 45% (prior to the leukapheresis) Sex
10. Female: Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (i.e., with a failure rate of \< 1% per year), preferably with low user dependency during the intervention period and for at least 6 months after the last infusion of MT-601 and agrees not to donate eggs (i.e., ova and oocytes) for the purpose of reproduction during this period
11. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 6 months after the last infusion of MT-601:

* Patients are excluded from the study if any of the following criteria apply:
1. Evidence of bulky disease at the time of the conditioning regimen (≥ 10 cm in diameter for LBCL or HL and \> 6 cm for other subtypes)
2. Untreated or ongoing treatment for CNS lymphoma or completed treatment within 2 weeks of apheresis (Note: May be allowed in Dose Expansion if disease specific cohort for CNS lymphoma is opened)
3. Refractory to CAR T therapy defined as a best response of stable disease or disease progression (Note: May be allowed in Dose Expansion if disease specific cohort for CAR T cell therapy refractory is opened)
4. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression Medical Conditions
5. Primary immunodeficiency
6. Severe or uncontrolled autoimmune disorder
7. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
8. Unresolved immune effector cell-associated neurotoxicity syndrome (ICANS) from prior CAR T cell administration. Consideration for Grade 1 may be made after discussion with the Medical Monitor
9. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast, and/or prostate) unless disease free for at least 3 years
10. Cardiac conditions:
1. Medically uncontrolled hypertension (≥ 160 mmHg systolic blood pressure or ≥ 100 mmHg diastolic blood pressure)
2. Congestive heart failure Class ≥ II as defined by the New York Heart Association
3. Acute coronary syndrome (including unstable angina, coronary artery stenting, or angioplasty, bypass grafting within prior 6 months)
4. History or evidence of current, uncontrolled, clinically significant, unstable arrhythmias
11. Oxygen saturation at room air \< 92%
12. Participant has known human immunodeficiency virus (HIV) infection, or active hepatitis B virus (HBV)/hepatitis C virus (HCV) infection
13. Acute bacterial, viral, fungal infection requiring systemic therapy (uncomplicated urinary tract infection and bacterial pharyngitis are permitted if responding to therapy)
14. History of severe allergic reactions to any of the study intervention components including conditioning regimen, dimethyl sulfoxide (DMSO) or to tocilizumab
15. Clinically significant reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline
* Participants with Grade 2 neuropathies due to prior treatment will be allowed on study.
* Participants with clinical nonsignificant toxicities, such as alopecia, will be allowed on study.
16. Receipt of allogeneic hematopoietic cell transplant (HCT) within 12 months; on immunosuppression or with evidence of donor/mixed chimera
17. Receipt of autologous HCT within 3 months
18. Treatment with CD19-directed CAR T cell therapy within 3 months
19. Treatment with bispecific antibody within 1 month
20. Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days
21. Treatment with monoclonal antibodies impacting T cell function within 14 days
22. Treatment with systemic immunosuppression including systemic corticosteroids (unless ≤5 mg/day oral prednisone or steroid equivalent) within 14 days
23. Treatment with chemotherapy within 7 days
24. Treatment with a live, attenuated vaccine within 4 weeks
25. Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days
26. Treatment with chemotherapy or biologics/monoclonal antibodies within 14 days
27. Treatment with radiation therapy within 7 days
28. Treatment with a tyrosine kinase inhibitor (TKI) within 7 days or 5 half-lives (whichever is longer) before conditioning regimen
29. Hematopoietic growth factors \<2 days
30. Treatment with experimental CAR T cell product unless approved by Medical Monitor
31. Treatment with other cancer therapy including investigational agents that do not fit in the above categories within 14 days
32. Major surgery within 14 days
33. Pregnant or lactating
34. Any other issue which, in the opinion of the treating physician, would make the participant ineligible for the study

Contacts and Locations

Study Contact

Monic Stuart, MD

CONTACT

1.650.868.6621

mstuart@markertherapeutics.com

Patricia Allison

CONTACT

1 (717) 471-5205

pallison@markertherapeutics.com

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

Colorado Blood Cancer Institute (Sarah Cannon)

Denver, Colorado, 80218

United States

University of Kansas Medical Center

Kansas City, Kansas, 66160

United States

Cornell

New York, New York, 10065

United States

Tennessee Oncology PLLC

Nashville, Tennessee, 37203

United States

Sarah Cannon Research Institute at St. David's South Austin

Austin, Texas, 78704

United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Marker Therapeutics, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-01-02

Study Completion Date2028-02-28

Study Record Updates

Study Start Date2023-01-02

Study Completion Date2028-02-28

Terms related to this study

Keywords Provided by Researchers

NHL
Lymphoma

Additional Relevant MeSH Terms

Non-Hodgkin Lymphoma, Adult
Non-Hodgkin Lymphoma, Refractory
Non-Hodgkin Lymphoma, Relapsed
Non Hodgkin Lymphoma
Hodgkin Lymphoma
Hodgkin Lymphoma, Adult
Hodgkin's Lymphoma, Relapsed, Adult