Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Diseases

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

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All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Lenalidomide

Idecabtagene vicleucel

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m2 and fludarabine 30mg/m2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x106 cells. Maintenance lenalidomide, starting at 10mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.

Lenalidomide and bb2121

Marcelo C Pasquini, MD, MS

Alfred Garfall, MD

Sergio Giralt, MD

This study is designed as a Phase II, multicenter, single arm trial to assess anti-B Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T-cells (bb2121) to improve post autologous hematopoietic cell transplant (HCT) responses among patients with multiple myeloma (MM).

After meeting the eligibility criteria and enrolling on the trial, patients will undergo leukapheresis for collection of autologous lymphocytes, which will be sent to BMS/Celgene manufacturing facilities. Once cells have been manufactured, patients will then proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m2 and fludarabine 30mg/m2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x106 cells. Maintenance lenalidomide, starting at 10mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression

Assess anti-B Cell Maturation Antigen(BCMA) chimeric antigen receptor (CAR) T-cells (bb2121) to improve post autologous hematopoietic cell transplant (HCT) responses among patients with multiple myeloma (MM).

MM CAR-T to Upgrade Response BMTCTN1902

Phase II Multicenter Trial of Anti-BCMA CAR T-Cell Therapy for MM Patients With Sub-Optimal Response After Auto HCT and Maintenance Len. BMTCTN1902

Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc., where indicated).

All Grade 3 or higher toxicities will be tabulated. The proportion of patients experiencing cytokine release syndrome CRS will be reported including overall and grades 3-4 based on the ASTCT grading

incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient

The feasibility of resuming maintenance following enrollment by 180 days after CAR T-cell infusion will be described. The proportion of patients initiating maintenance at 180 days following bb2121 infusion will be reported.

The event is death from any cause. The time to this event is the time from initial enrollment to sdeath, loss to follow-up, or the end of the study, whichever comes first.

Quantitation of CAR T-cells in peripheral blood will be determined at specified timepoints by quantitative PCR assay, measured in copies/mcg genomic DNA. Peak CAR T-cell expansion will be compared between subjects who are and are not in CR at 12 months, and between subjects who are and are not progression-free at 12 months.

Quantitation of CAR T-cells in peripheral blood will be determined at specified timepoints by quantitative PCR assay, measured in copies/mcg genomic DNA. Persistence will be measured in 2 ways: 1) as an area under the curve (AUC) over first 6 months post CAR T-cell infusion; and 2) as still having detectable CAR T-cells at 6 months post CAR T-cell infusion. AUC6mos and 6- month persistence will be compared between subjects who are and are not in CR at 12 months, and between subjects who are and are not progression-free at 12 months.

BCMA expression at specified timepoints will be determined by immunohistochemical staining of bone marrow biopsy specimens and/or flow cytometric analysis of bone marrow aspirate material, in order to assess for baseline expression and potential loss of expression post-treatment. Both percent of MM cells that stain positive as well as staining intensity will be reported.

The cellular composition of marrow (T-Cells, B-Cells, Natural Killer Cells, dendritic cells, and myeloid derived suppressor cells) will be quantified at the specified timepoints by flow cytometry.

Achieving a complete response or better (CR or sCR) as assessed by the 6-month time point after BCMA CAR T-cell therapy in MM patients with suboptimal disease responses after an autologous HCT and lenalidomide maintenance.

Diseases will be assessed by response categories based on the International Myeloma Working Group: Stringent Complete Response (sCR), Complete Remission (CR), Very Good Partial Remission (VGPR), Partial Remission (PR), Minimal Response (MR), Stable Disease (SD).

: Proportion of patients achieving upgrade in response following enrollment (SD to MR or greater, MR to PR or greater, or PR to VGPR or greater) and Conversion to MRD negativity. MRD will be assessed by multi-color flow at 10-5 level

Non-Relapse Mortality (NRM) is defined as death occurring in a patient from causes other than disease relapse or progression. Disease progression is the competing event for NRM.

Defined as progression of disease or death from any cause. Surviving patients without disease progression will be censored at the date of last contact.

Overall incidence of CRS of any grade and grade 3 or 4 CRS post CAR T-cell infusion will be reported on all patients.

Overall incidence of prolonged cytopenias will be reported. Prolonged cytopenia is defined as failure to achieve ANC greater than 500/mm3 or platelet count greater than 20,000/mm3(with or without support) by 30 days post CAR T-cell ifusion.

Overall incidence of CAR T-cell related neurotoxicity per the ASBMT immune effector cell associated neurotoxicity syndrome (ICANS) Consesus Grading.

Spots Global Cancer Trial Database for lenalidomide and bb2121