RECRUITING

TriPRIL CAR T Cells in Multiple Myeloma

Conditions

Multiple Myeloma Multiple Myeloma in Relapse Refractory Multiple Myeloma

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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 research study involves the study of TriPRIL CAR T Cells for treating people with relapsed or refractory multiple myeloma and to understand the side effects when treated with TriPRIL CAR T Cells. This research study involves the study drugs:. * TriPRIL CAR T Cells * Fludarabine and Cyclophosphamide: Standardly used chemotherapy drugs as part of lymphodepleting process

Official Title

A Phase I Clinical Trial With TriPRIL CAR T Cells for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma

Quick Facts

Study Start:2021-10-05

Study Completion:2028-01-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05020444

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

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Ability to understand and the willingness to sign a written informed consent document. * Age ≥18 years at the time of signing informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Life expectancy of greater than 12 weeks * Histologically or cytologically confirmed diagnosis of relapsed/refractory multiple myeloma. Documented measurable disease includes at least one or more of the following criteria: * Serum M-protein ≥0.5 g/dL * Urine M-protein ≥200 mg/24 hours * Involved serum free light chain ≥100 mg/L with abnormal κ/λ ratio * More than one extramedullary lesion on imaging, including at least one lesion that is 1cm or greater in size and able to be followed by imaging assessments * Bone marrow plasma cells ≥30% * Relapsed/refractory multiple myeloma with at least 3 prior regimens of systemic therapy including proteasome inhibitor, IMiDs and anti-CD38 antibody; or has "triple-refractory" disease following treatment with proteasome inhibitor, IMiD and anti-CD38 antibody, as part of the same or different regimens. * Adequate organ and marrow function as defined below: * O2 saturation ≥92% on room air while awake * LVEF ≥40% by ECHO or MUGA scan * ANC ≥1.0k/μl, PLT ≥50k/μl, (NOTE: Platelet transfusion not allowed within 7 days; growth factor neupogen not allowed within 7 days, neulasta within 14 days) * Creatinine clearance ≥50 mL/min and not on dialysis * AST/ALT \<3 x ULN * Direct bilirubin \<1.5 x ULN (allow x 3 ULN for Gilbert's syndrome) * PTT, PT/INR \<1.5 x ULN, unless on a stable dose of anti-coagulant for a thromboembolic event (Patients with any history of thromboembolic stroke; or history or Grade 2 or greater hemorrhage within 60 days are excluded) * Resolution of AEs from any prior therapy (G2 alopecia and G2 sensory neuropathy are allowed, cytopenias allowed per eligibility criteria above) * Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * The effects of TriPRIL CAR T cells on the developing human fetus are unknown. Male and female participants of childbearing potential must agree to use highly effective methods of birth control prior to study entry, for the duration of study participation, and through 6 months after completion of TriPRIL CAR T cells administration. 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. * Total abstinence * Female sterilization (tubal ligation, bilateral oophorectomy, and/or hysterectomy) * Male sterilization, at least 6 months prior to screening * Intrauterine device * Oral, injected, or implanted hormonal contraception AND barrier methods of contraception * Willing to comply with and able to tolerate study procedures, including Long-term Safety Follow-up lasting up to 15 years per FDA guidance * Subject's apheresis product from non-mobilized cells is received and accepted for cell processing by manufacturing site.	* Treatment with any of the following therapies as specified below: * Any prior systemic treatment for multiple myeloma within the 14 days prior to scheduled leukapheresis unless discussed with the medical monitor * Receiving high-dose (e.g., \>10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to leukapheresis * Autologous stem cell transplantation within 3 months prior to leukapheresis * Any prior allogeneic stem cell transplantation * Other CAR-T cell therapy within 6 months of leukapheresis * Plasma cell leukemia or history of plasma cell leukemia * Patients with solitary plasmacytomas without evidence of other measurable disease * History of allergic reactions attributed to compounds of similar chemical or biologic composition to CAR- T cells * Contraindication to the protocol-specified doses of fludarabine or cyclophosphamide * Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia and grade ≤2 sensory neuropathy. * Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, e.g., related to disease) * Symptomatic congestive heart failure * Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months prior to screening Significant pulmonary dysfunction * Auto-immune disease requiring immunosuppressive therapy * Pulmonary embolism or DVT within three months of enrollment or uncontrolled thromboembolic events. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of DVT or PE if greater than three months from time of enrollment. Prophylactic anticoagulation is allowed. * Recent severe hemorrhage (within the past 60 days) * Seropositive for and with evidence of active hepatitis B or C infection at time of screening, or HIV seropositive * Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months are eligible * Subjects seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible * Subjects who had hepatitis C but have received antiviral therapy and show no detectable HCV viral RNA for 6 months are eligible * Active central nervous system (CNS) involvement by malignancy. NOTE: subjects who are asymptomatic, stable, and received prior effective treatment for CNS disease may be eligible after discussion with the medical monitor. * Any sign of active or prior CNS pathology including history of epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis. * Active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the medical monitor. * Females who are pregnant or breastfeeding or females of childbearing potential not using an effective method of birth control * Subjects with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the subject at unacceptable risk * Participants taking any other medicine concurrently that may interfere with the study (need to consult with the principle investigator)

Inclusion Criteria

Exclusion Criteria

* Ability to understand and the willingness to sign a written informed consent document.
* Age ≥18 years at the time of signing informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Life expectancy of greater than 12 weeks
* Histologically or cytologically confirmed diagnosis of relapsed/refractory multiple myeloma. Documented measurable disease includes at least one or more of the following criteria:
* Serum M-protein ≥0.5 g/dL
* Urine M-protein ≥200 mg/24 hours
* Involved serum free light chain ≥100 mg/L with abnormal κ/λ ratio
* More than one extramedullary lesion on imaging, including at least one lesion that is 1cm or greater in size and able to be followed by imaging assessments
* Bone marrow plasma cells ≥30%
* Relapsed/refractory multiple myeloma with at least 3 prior regimens of systemic therapy including proteasome inhibitor, IMiDs and anti-CD38 antibody; or has "triple-refractory" disease following treatment with proteasome inhibitor, IMiD and anti-CD38 antibody, as part of the same or different regimens.
* Adequate organ and marrow function as defined below:
* O2 saturation ≥92% on room air while awake
* LVEF ≥40% by ECHO or MUGA scan
* ANC ≥1.0k/μl, PLT ≥50k/μl, (NOTE: Platelet transfusion not allowed within 7 days; growth factor neupogen not allowed within 7 days, neulasta within 14 days)
* Creatinine clearance ≥50 mL/min and not on dialysis
* AST/ALT \<3 x ULN
* Direct bilirubin \<1.5 x ULN (allow x 3 ULN for Gilbert's syndrome)
* PTT, PT/INR \<1.5 x ULN, unless on a stable dose of anti-coagulant for a thromboembolic event (Patients with any history of thromboembolic stroke; or history or Grade 2 or greater hemorrhage within 60 days are excluded)
* Resolution of AEs from any prior therapy (G2 alopecia and G2 sensory neuropathy are allowed, cytopenias allowed per eligibility criteria above)
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* The effects of TriPRIL CAR T cells on the developing human fetus are unknown. Male and female participants of childbearing potential must agree to use highly effective methods of birth control prior to study entry, for the duration of study participation, and through 6 months after completion of TriPRIL CAR T cells administration. 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.
* Total abstinence
* Female sterilization (tubal ligation, bilateral oophorectomy, and/or hysterectomy)
* Male sterilization, at least 6 months prior to screening
* Intrauterine device
* Oral, injected, or implanted hormonal contraception AND barrier methods of contraception
* Willing to comply with and able to tolerate study procedures, including Long-term Safety Follow-up lasting up to 15 years per FDA guidance
* Subject's apheresis product from non-mobilized cells is received and accepted for cell processing by manufacturing site.

* Treatment with any of the following therapies as specified below:
* Any prior systemic treatment for multiple myeloma within the 14 days prior to scheduled leukapheresis unless discussed with the medical monitor
* Receiving high-dose (e.g., \>10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to leukapheresis
* Autologous stem cell transplantation within 3 months prior to leukapheresis
* Any prior allogeneic stem cell transplantation
* Other CAR-T cell therapy within 6 months of leukapheresis
* Plasma cell leukemia or history of plasma cell leukemia
* Patients with solitary plasmacytomas without evidence of other measurable disease
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CAR- T cells
* Contraindication to the protocol-specified doses of fludarabine or cyclophosphamide
* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia and grade ≤2 sensory neuropathy.
* Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, e.g., related to disease)
* Symptomatic congestive heart failure
* Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months prior to screening Significant pulmonary dysfunction
* Auto-immune disease requiring immunosuppressive therapy
* Pulmonary embolism or DVT within three months of enrollment or uncontrolled thromboembolic events. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of DVT or PE if greater than three months from time of enrollment. Prophylactic anticoagulation is allowed.
* Recent severe hemorrhage (within the past 60 days)
* Seropositive for and with evidence of active hepatitis B or C infection at time of screening, or HIV seropositive
* Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months are eligible
* Subjects seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible
* Subjects who had hepatitis C but have received antiviral therapy and show no detectable HCV viral RNA for 6 months are eligible
* Active central nervous system (CNS) involvement by malignancy. NOTE: subjects who are asymptomatic, stable, and received prior effective treatment for CNS disease may be eligible after discussion with the medical monitor.
* Any sign of active or prior CNS pathology including history of epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis.
* Active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the medical monitor.
* Females who are pregnant or breastfeeding or females of childbearing potential not using an effective method of birth control
* Subjects with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the subject at unacceptable risk
* Participants taking any other medicine concurrently that may interfere with the study (need to consult with the principle investigator)

Contacts and Locations

Study Contact

Matthew J Frigault, MD

CONTACT

(617) 643-6175

MFRIGAULT@partners.org

Principal Investigator

Matthew J Frigault, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114

United States

Collaborators and Investigators

Sponsor: Marcela V. Maus, M.D.,Ph.D.

Matthew J Frigault, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

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 Date2021-10-05

Study Completion Date2028-01-01

Study Record Updates

Study Start Date2021-10-05

Study Completion Date2028-01-01

Terms related to this study

Keywords Provided by Researchers

Multiple Myeloma
Multiple Myeloma in Relapse
Refractory Multiple Myeloma

Additional Relevant MeSH Terms

Multiple Myeloma
Multiple Myeloma in Relapse
Refractory Multiple Myeloma