B Cell LymphomasPhase 1MicroBLITZNCT03920631
Microtransplantation and Checkpoint Blockade Immunotherapy for Relapsed or Refractory B Cell Lymphomas
A Phase 1 study testing Nivolumab and Microtransplantation in people with B Cell Lymphomas, run by Ahmed Galal, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B Cell Lymphomas
- What is being tested?
- Nivolumab and Microtransplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2020to 15 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, and men who are sexually active must use effective methods of contraception from the time of enrollment to 1 month after last therapy administered as part of the protocol.
- Must have biopsy-proven primary refractory disease or relapsed disease after frontline therapy.
- Adequate organ function parameters:
- Renal function: Creatinine clearance ≥ 45ml/min (Cockrauft-Gault Formula)
- Liver function:
- AST/ALT ≤ 3x the institutional ULN.
- Total bilirubin ≤ 2x the institutional ULN with the exception of patients with Gilbert syndrome; patients with Gilbert syndrome may be included if their total bilirubin is ≤ 3.0x ULN and direct bilirubin is ≤ 2x ULN
- Pulmonary function: PFTs with DLCO ≥ 40%.
- Cardiac function: Must have LVEF ≥ 40% confirmed by echocardiogram or MUGA scan.
- Bone marrow reserve without transfusion defined as:
- Absolute neutrophil count (ANC) ≥ 1,000/mm3
- Platelets ≥ 50,000/mm3
- Subjects must have a potential 3-5/6 HLA-matched (A, B, DRB1) related haploidentical donor (either a first or second- degree relative) that will be evaluated for eligibility to provide hematopoietic cells for infusion.
Who cannot join
- 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).
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- 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).
- History of solid organ transplantation.
- Pregnant or lactating women.
- Prisoners or those compulsorily detained.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: MicroBLITZ: Microtransplantation and Checkpoint Blockade Immunotherapy for Relapsed or Refractory B Cell Lymphomas
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.
Read the detailed description
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.
- Conditions
- B Cell Lymphomas
- Being tested
- Nivolumab, Microtransplantation
- Keywords
- B Cell Lymphomas, Microtransplantation, Nivolumab
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called OPDIVO™, BMS-936558, MDX1106, ONO-4538
Nivolumab (1 mg/Kg or 3 mg/kg) every 2 weeks per cohort dose level and schedule
MicrotransplantationBiological
HLA-mismatched peripheral blood stem cells
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Microtransplantation (MST) | Experimental | MST:Infusion of granulocyte colony stimulating factor (G-CSF) mobilized HLA-mismatched peripheral blood stem cells (GPBSC) Receives: 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). Receives: 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). Receives: Drug: Nivolumab; Biological: Microtransplantation |
| Cohort 4: Expansion | Experimental | Microtransplantation (Day 0) + nivolumab (at RP2D) Receives: Drug: Nivolumab; Biological: Microtransplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 4 years
Number of subjects experiencing AE
Measured: 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.
Measured: 2.5 years
Progression-free Survival (PFS)
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
Measured: 4 years
Overall Survival
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.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study start10 Jul 2020 (estimated)
- Primary completion15 Mar 2023 (estimated)
- Study completion15 May 2023 (estimated)
Why it stopped: Lack of accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B Cell LymphomasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ahmed Galal, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ahmed Galal, MD, Duke University
- Investigators
- Ahmed Galal, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03920631
- Sponsor's protocol ID
- Pro00101349
- Acronym
- MicroBLITZ
- Status last verified
- Mar 2021
- First submitted
- 8 Apr 2019
- Last updated
- 23 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MicroBLITZ: Microtransplantation and Checkpoint Blockade Immunotherapy for Relapsed or Refractory B Cell Lymphomas
- ClinicalTrials.gov ID
- NCT03920631
- Acronym / sponsor ID
- MicroBLITZ / Pro00101349
- Conditions
- B Cell Lymphomas
- Keywords
- B Cell Lymphomas, Microtransplantation, Nivolumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ahmed Galal, MDUniversity, hospital or other
- Study start
- 10 Jul 2020 (estimated)
- Primary completion
- 15 Mar 2023 (estimated)
- Study completion
- 15 May 2023 (estimated)
- First posted
- 19 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Microtransplantation (MST) | Experimental | Biological: MicrotransplantationMST:Infusion of granulocyte colony stimulating factor (G-CSF) mobilized HLA-mismatched peripheral blood stem cells (GPBSC) |
| Cohort 2/2b: MST + Nivolumab | Experimental | Drug: Nivolumab, Biological: Microtransplantation2: 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). |
| Cohort 3/3b: MST + Nivolumab | Experimental | Drug: Nivolumab, Biological: Microtransplantation3: 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). |
| Cohort 4: Expansion | Experimental | Drug: Nivolumab, Biological: MicrotransplantationMicrotransplantation (Day 0) + nivolumab (at RP2D) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Patients with relapsed/refractory B cell lymphomas of the following subtypes:
- 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.
Key exclusion criteria (18 listed)
- Prior Treatments:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OPDIVO™, BMS-936558, MDX1106, ONO-4538Nivolumab (1 mg/Kg or 3 mg/kg) every 2 weeks per cohort dose level and schedule | Drug | Cohort 2/2b: MST + Nivolumab, Cohort 3/3b: MST + Nivolumab, Cohort 4: Expansion |
| MicrotransplantationHLA-mismatched peripheral blood stem cells | Biological | Cohort 1: Microtransplantation (MST), Cohort 2/2b: MST + Nivolumab, Cohort 3/3b: MST + Nivolumab, Cohort 4: Expansion |
Primary outcome
Maximum Tolerated Dose of nivolumab in combination with Microtransplantation
Time frame: 1.5 years
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.
Incidence of dose limiting toxicity (DLT)
Time frame: 4 years
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).
Number of subjects experiencing AE
Time frame: 4 years
3 secondary outcomes
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.
Time frame: 2.5 years
Progression-free Survival (PFS)
Time frame: 4 years
Overall Survival
Time frame: 4 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmed Galal, MD principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab and Microtransplantation in people with B Cell Lymphomas, run by Ahmed Galal, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose of nivolumab in combination with Microtransplantation (time frame: 1.5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2021.