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

NCT03920631 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Pro00101349
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

B Cell Lymphomas

Keywords

B Cell Lymphomas; Microtransplantation; Nivolumab

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose of nivolumab in combination with Microtransplantation

  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.

  1.5 years

• Incidence of dose limiting toxicity (DLT)

  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).

  4 years

• Number of subjects experiencing AE

  4 years

Secondary Outcomes (3)

• Overall response rate (%) is defined as the number of patients achieving a complete response or partial response as a proportion of total patients evaluable for response.

  2.5 years

• Progression-free Survival (PFS)

  4 years

• Overall Survival

  4 years

Study Arms (4)

Cohort 1: Microtransplantation (MST)

EXPERIMENTAL

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

Biological: Microtransplantation

Cohort 2/2b: MST + Nivolumab

EXPERIMENTAL

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).

Drug: Nivolumab; Biological: Microtransplantation

Cohort 3/3b: MST + Nivolumab

EXPERIMENTAL

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).

Drug: Nivolumab; Biological: Microtransplantation

Cohort 4: Expansion

EXPERIMENTAL

Microtransplantation (Day 0) + nivolumab (at RP2D)

Drug: Nivolumab; Biological: Microtransplantation

Interventions

Nivolumab DRUG

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

Also known as: OPDIVO™, BMS-936558, MDX1106, ONO-4538

Cohort 2/2b: MST + Nivolumab; Cohort 3/3b: MST + Nivolumab; Cohort 4: Expansion

Microtransplantation BIOLOGICAL

HLA-mismatched peripheral blood stem cells

Cohort 1: Microtransplantation (MST); Cohort 2/2b: MST + Nivolumab; Cohort 3/3b: MST + Nivolumab; Cohort 4: Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed/refractory B cell lymphomas of the following subtypes:
• Diffuse large B-cell lymphoma (DLBCL)
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations (DHL/THL)
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (GZL)
• Primary mediastinal large B-cell lymphoma (PMBCL)
• Mantle cell lymphoma (MCL)
• Follicular lymphoma (FL)
• Marginal zone lymphoma (MZL)
• Lymphoplasmacytic Lymphoma / Waldenstrom Macroglobulinemia (LPL/WM)
• Hodgkin lymphoma (HL)
• Ability to provide written informed consent for the protocol and understand the investigational nature of the study.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other procedures.
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group performance status of ≤ 2.
• Evidence of at least one measurable lesion on imaging, defined as nodes/nodal masses \> 1.5 cm, extranodal masses \>1.0 cm or PET avid lesions consistent with lymphoma.

You may not qualify if:

• Prior Treatments:
• Prior treatment with allogeneic HSCT.
• Treatment with CAR-T cells within 6 months of study enrollment.
• Treatment with an immune checkpoint inhibitor within 3 months of study enrollment.
• Prior grade 3 or higher toxicities with immune checkpoint inhibitor use, excluding lymphopenia, asymptomatic amylase or lipase elevation or laboratory abnormalities that correct to grade 1 within 72 hours.
• Chemotherapy, radiation or surgical resection of malignancy within 2 weeks prior to the start of lymphodepleting chemotherapy (washout period).
• Active, uncontrolled serious infection or medical or psychiatric illness, that in the investigator's opinion is likely to interfere with participation in this clinical trial.
• Known active CNS involvement by malignancy.
• History of seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Active replication of hepatitis B or active hepatitis C (HCV RNA positive). Those with prior disease who are PCR negative at enrollment and meet liver function eligibility criterion are eligible.
• Known HIV positive patients.
• Patients with unstable angina and/or myocardial infarction within 6 months prior to screening.
• Cardiac arrhythmia not controlled with medical management, evidence of pericardial effusion on imaging that is compromising function.
• History of a second malignancy requiring treatment at any time within the 3 years prior to study enrollment. The following are allowed within 3 years of study enrollment if subject has received definitive local therapy (i.e., surgical excision, external beam radiation, or other local therapy with curative intent): non-melanoma skin cancers, organ-confined localized prostate cancer treated with curative intent, or carcinoma in situ.
• Active autoimmune disease, history of primary immunodeficiency, or any syndrome that requires systemic corticosteroids or immunosuppressive medications (excluding Hashimoto's thyroiditis, vitiligo, or DM type I).

Sponsors & Collaborators

• Ahmed Galal, MD: lead

Study Sites (1)

Duke University

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ahmed Galal, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Instructor in the Department of Medicine

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 19, 2019
• Study Start: July 10, 2020
• Primary Completion: March 15, 2023
• Study Completion: May 15, 2023
• Last Updated: March 23, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)