Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Antineoplastic Agents

Morphine

Immunomodulating Agents

Nivolumab

Lenograstim

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

MST:Infusion of granulocyte colony stimulating factor (G-CSF) mobilized HLA-mismatched peripheral blood stem cells (GPBSC)

2: Microtransplantation (Day 0) + nivolumab (3 mg/kg) every 2 weeks (beginning on Day+14)

2b: Microtransplantation (Day 0) + nivolumab (1 mg/kg) every 2 weeks (beginning on Day+14).

3: Microtransplantation (Day 0) + nivolumab (3 mg/kg) every 2 weeks (beginning on Day-1).

3b: Microtransplantation (Day 0) + nivolumab (1 mg/kg) every 2 weeks (beginning on Day-1).

Microtransplantation (Day 0) + nivolumab (at RP2D)

Nivolumab (1 mg/Kg or 3 mg/kg) every 2 weeks per cohort dose level and schedule

HLA-mismatched peripheral blood stem cells

Microtransplantation

Ahmed Galal, MD

The purpose of this study is to find out if microtransplantation (MST) in combination with nivolumab is safe and effective in patients with relapsed or refractory B cell lymphomas.

This is a non-randomized, open-label, phase 1 study to assess the safety of nivolumab (OPDIVO™, also referred to as BMS-936558, MDX1106, and ONO-4538) in combination with microtransplantation (MST) in patients ≥ 18 years of age with relapsed or refractory B cell lymphomas. A conventional cohorts-of-3 dose-escalation phase I design will be used to determine the optimal dosing strategy of nivolumab in combination with MST. The safety of microtransplantation without nivolumab will be evaluated at the first dose level. If significant, unexpected toxicity is observed at Dose Levels 2 or 3, subsequent cohorts will switch to the alternate dosing schedule to evaluate the safety of dose-reduced nivolumab. After determination of the maximum tolerated dose level, patients will be recruited into an expansion cohort at that level.

Microtransplantation and Checkpoint Blockade Immunotherapy for Relapsed or Refractory B Cell Lymphomas

MicroBLITZ: Microtransplantation and Checkpoint Blockade Immunotherapy for Relapsed or Refractory B Cell Lymphomas

In the dose escalation portion, patients will be sequentially enrolled in 3 cohorts at dose levels in a standard 3+3 design until the maximum tolerated dose (MTD) of nivolumab in combination with microtransplantation is reached.

The MTD will be defined as the dose level where at most 1 out of 6 patients experience a dose limiting toxicity (DLT) and will also be the recommended phase 2 dose (RP2D) strategy.

Dose limiting toxicity will be estimated based on the incidence and intensity of drug related adverse events (AEs) due to microtransplantation and/or nivolumab infusion. DLT will be graded according to the NCI CTCAE version 5.0 criteria and GVHD will be graded by consensus criteria (Przepiorka D et al, BMT, 1995).

progression-free survival (PFS) is defined as the time interval from the time of enrollment on this study to the date of progressive disease (PD) or death, whichever is first reported. Patients are evaluable for PFS if they receive any treatment as part of this study. One- and two-year PFS estimates will also be calculated

Overall Survival (OS) is defined as the time interval from the time of enrollment in this study to the date of death from any cause. If the subject is alive or the vital status is unknown, OS will be censored at the date that the subject is last known to be alive, or their last contact date. One- and two-year survival estimates will be generated.

Instructor in the Department of Medicine

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Antibodies

Immunoglobulins

Subjects who have previously been treated with an ACTR T cell product

ACTR T Cell Product

Jessica Sachs, MD

Subjects treated with an ACTR product may participate in this long-term follow-up study after the completion of the final scheduled visit in the parent clinical study or other investigational setting, such as compassionate use, named patient Investigational New Drug application, expanded access program, or equivalent setting. No investigational product or treatment will be administered in this study. These subjects will be followed for safety monitoring on a schedule of decreasing frequency through 15 years post-ACTR treatment, in accordance with US FDA Regulatory guidance pertaining to long-term safety follow-up for study subjects receiving recombinant DNA-containing investigational products.

Blood for replication competent retrovirus (RCR) testing

Remaining biological samples from other protocol procedures (e.g., blood for presence of ACTR+ T cells) may also be stored, at the discretion of the sponsor, for potential future biomarker analyses of T cells, DNA, RNA, and other cells or molecules to study immunology or gene therapy.

Optional blood, bone marrow, and tissue samples also may be collected in the event of a subject's death if an autopsy is performed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Microtransplantation and Checkpoint Blockade Immunotherapy for Relapsed or Refractory B Cell Lymphomas	NCT03920631	B Cell Lymphoma...	Nivolumab Microtransplant...	18 Years -	Duke University
Long-Term Follow-Up Study of Subjects Treated With ACTR T Cell Product	NCT02840110	B Cell Lymphoma... Multiple Myelom... Solid Tumor HER-2 Protein O...	ACTR T Cell Pro...	18 Years -	Cogent Biosciences, Inc.

Spots Global Cancer Trial Database for b cell lymphomas