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Multiple MyelomaPhase 1NCT03524235

Haploidentical Stem Cell Transplant with Prophylactic Natural Killer DLI for Lymphoma, Multiple Myeloma, and CLL

A Phase 1 study testing Total Body Irradiation, Haploidentical Stem Cell Transplantation and CD56-Enriched Donor Lymphocyte Infusion in people with Multiple Myeloma and CLL, run by Noah Merin at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study seeks to examine the investigational use of the conditioning regimen (bendamustine, fludarabine, and rituximab) prior to haploidentical peripheral blood allogeneic stem cell transplantation with Post-Transplant Cyclophosphamide. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Total Body Irradiation, Haploidentical Stem Cell Transplantation and CD56-Enriched Donor Lymphocyte Infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
18 Jul 2018to 6 Nov 2024
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of resistant or relapsed CLL, Non-Hodgkin Lymphoma, Hodgkin Lymphoma, T-cell lymphoma, NK or NK/T Lymphoma.
  • Meets one of the following criteria:
  • relapsed after auto-transplant, or
  • failed to mobilize autologous stem cells, or
  • for whom allogeneic stem cell transplant is deemed appropriate given disease risk factors that make cure with autologous transplant seem unlikely, such as history of chemotherapy refractoriness, high risk disease features/mutations/translocations (e.g., Double Hit / Double Expressor DLBCL), short remission after prior chemotherapy, or histologic transformation (see below).
  • For Patients with Aggressive Mantle Cell and Diffuse Large B Cell Lymphoma who have not had a prior autologous transplant:
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  • Must have received at least 2 lines of prior therapy, and
  • Have been exposed to anthracycline, and
  • High and High-Intermediate aaIPI score (2 or 3 factors), and
  • Have relapsed within one year of primary therapy
  • For diagnosis of other aggressive lymphoma (e.g. NK/T Lymphoma, T Cell
  • Lymphoma, etc.):
  • Must have received at least 2 lines of prior therapy, and
  • Relapsed within 12 months of most recent therapy
  • For low-grade lymphomas / CLL:
  • Standard risk patients (absence of del(17p), absence of del(11q), no TP53 mutation and absence of complex karyotype) must have progressed on BCR inhibitor, or undergone histologic transformation, to be eligible.
  • Patients with high risk disease (del(17p) or TP53 mutations and/or complex phenotype) who relapse after frontline therapy, demonstrate refractory disease to second line therapy (not BCR inhibitors), but show an objective response to BCR inhibitors are eligible to be taken off BCR inhibitors in order to proceed to alloHSCT on trial. Patients with high risk disease who relapse after frontline therapy, demonstrate refractory disease to second line therapy including BCR inhibitors (not BCL-2 inhibitors), but show an objective response to BCL-2 inhibitors (venetoclax) are eligible to be taken off BCL-2 inhibitors in order to proceed to alloHSCT on trial.
  • For aggressive lymphomas, partial or complete remission (PR or CR) is required prior to alloHSCT.
  • Regarding CD20 expression: Patients with B cell malignancies that were CD20+ at any level at the time of relapse diagnosis (including partial / dim staining on IHC or partial / low level expression by flow cytometry) will receive rituximab as part of allogeneic transplant conditioning, if indicated. Patients with primary-refractory disease who were CD20+ at any level at the time of diagnosis will likewise receive rituximab, if indicated. Patients with histologies that were CD20- will not receive rituximab (T cell lymphoma, NK/T lymphoma, etc.). Fresh tissue / repeat biopsy is not required; the most recent biopsy will be reviewed to assess CD20 status.
  • Patient age 18 - 75 years with:
  • Early relapse (less than 24 months) after primary therapy that included an autologous HSCT, or
  • High risk multiple myeloma defined as t(4;14), del(17p), -13, t(14;16), amp (1q21), chromosome 8q24.1/c-MYC abnormality, or LDH > ULN at diagnosis, provided patients respond favorably to salvage therapy before enrollment for alloHSCT on trial and patient is age < 55, or
  • Patients failing to mobilize peripheral blood stem cells for autologous transplantation, or
  • Extramedullary disease at diagnosis or relapse, or
  • Plasma-cell leukemia with chemosensitive disease
  • Inclusion Criteria - Control Patients (specimen collection, only)
  • Age 18-75 years
  • Undergoing standard-of-care reduced-intensity peripheral blood allogeneic stem cell transplantation (any indication, donor source, conditioning regimen) using PTCy GVHD prophylaxis.
  • Willing to provide longitudinal blood samples per Control Specimen Collection Calendar for correlative studies (for comparison to specimens from patients treated on the trial).
  • Agrees to let study personnel collect excess bone marrow aspirate whenever a bone marrow biopsy is performed for clinical purposes, and use for research.

Who cannot join

  • Patient has a readily-available, suitable, fully-matched sibling donor (MRD) less than age 55. 'Suitable' means no high-titre donor-specific antibodies present, and negative IDM testing with no contraindications.
  • Patient has a clinically-significant donor-specific antibody for the selected donor (DSA clearance is not allowed).
  • Poor cardiac function: left ventricular ejection fraction <45% as determined by MUGA or ECHO.
  • Symptomatic pulmonary disease. Poor pulmonary function: FEV1, FVC, and DLCO <50% predicted (corrected for hemoglobin) for patients who have not received thoracic or mantle irradiation. For patients who have received thoracic or mantle irradiation, FEV1 and FVC <70% predicted or DLCO < 50 of predicted.
  • Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy). ALT or AST > 5 x laboratory upper normal limits.
  • Poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 60 mL/min based on Traditional Cockcroft-Gault formula
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  • Women of childbearing potential who currently are pregnant (Β-HCG+) or who are not practicing adequate contraception.
  • Uncontrolled viral, bacterial, or fungal infections. Patients with symptoms consistent with RSV, influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay).
  • Uncontrolled CNS involvement by malignancy (patients with prior history of CNS disease controlled with intrathecal chemotherapy or prior systemic therapy are allowed).
  • Patients who have any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up.
  • Exclusion Criteria - Control Patients (specimen collection, only)
  • Undergoing myeloablative alloHSCT.
  • Non-PTCy GVHD prophylaxis.
  • Non-PBSC transplant (bone marrow stem cell source).
  • Not willing to give longitudinal blood specimens for research use or not willing to allow access to medical records for non-clinical purposes.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

Other trials in United States

About this study

Official title: IIT2017-03-Merin-HaploBFR: Bendamustine, Fludarabine, and Rituximab Conditioning for Haploidentical Stem Cell Transplantation with CD56-Enriched Donor Cell Infusion for Relapsed/Refractory Lymphoma, Multiple Myeloma, and CLL

This study seeks to examine the investigational use of the conditioning regimen (bendamustine, fludarabine, and rituximab) prior to haploidentical peripheral blood allogeneic stem cell transplantation with Post-Transplant Cyclophosphamide. The study will also test the investigational use of CD56-enriched Donor Lymphocyte Infusion to see if this treatment is safe, and whether or not it will help patients achieve better outcomes post-transplant, including reduced risk of Graft-Versus-Host Disease (GVHD), and preventing disease relapse.

Read the detailed description

This is a single center Phase I trial of a new haploidentical stem cell transplant regimen intended to assess safety. Two groups of patients are planned: patients with lymphoma and patients with multiple myeloma. Each subject will receive a haploidentical stem cell transplantation using peripheral blood stem cells. Bendamustine-fludarabine-rituximab-TBI conditioning will be used, followed by stem cell infusion, with Post-Transplant Cyclophosphamide and tacrolimus for GVHD prophylaxis. Patients will receive a CD56-selected DLI on day +8. Evaluations will be taken at baseline and at each of the study visits. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study. Total duration of subject participation will be one year. Total duration of the study is expected to be three years.

Being tested
Total Body Irradiation, Haploidentical Stem Cell Transplantation, CD56-Enriched Donor Lymphocyte Infusion, Bendamustine, Fludarabine
Keywords
Relapsed/Refractory Lymphoma, Multiple Myeloma, CLL, Bendamustine, Haploidentical Stem Cell Transplantation, GVHD, Allogeneic Stem Cell Transplantation, Natural Killer Cell, CliniMACS, Post-transplantation cyclophosphamide, Donor Lymphocyte Infusion, Minimal Residual Disease, Hodgkin Lymphoma
Medical subject headings
Multiple Myeloma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Hodgkin Disease, Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Total Body IrradiationRadiation

    Also called TBI

    Pre-Transplantation Total Body Irradiation

  • Haploidentical Stem Cell TransplantationProcedure or surgery

    Haploidentical Stem Cell Transplantation

  • CD56-Enriched Donor Lymphocyte InfusionBiological

    CD56-Enriched Donor Lymphocyte Infusion

  • BendamustineDrug

    Also called Bendeka; Treanda

    Pre-Transplantation Bendamustine

  • FludarabineDrug

    Also called Fludara

    Pre-Transplantation Fludarabine

  • RituximabDrug

    Also called Rituxan

    Pre-Transplantation Rituximab (Rituximab for lymphoma diagnosis only)

Study groups in NCT03524235
Study groupRoleWhat they receive
SubjectsExperimentalPre-Transplantation Conditioning (Bendamustine, Fludarabine, and Rituximab + Total Body Irradiation) + Haploidentical Stem Cell Transplantation with CD56-enriched donor lymphocyte infusion
Receives: Radiation: Total Body Irradiation; Procedure: Haploidentical Stem Cell Transplantation; Biological: CD56-Enriched Donor Lymphocyte Infusion; Drug: Bendamustine; Drug: Fludarabine; Drug: Rituximab
ControlsNo interventionPatients undergoing standard-of-care reduced-intensity peripheral blood allogeneic stem cell transplantation (any indication, donor source, conditioning regimen) using PTCy GVHD prophylaxis.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Survival at 30 days post -transplantation

    Proportion of patients undergoing BFR-TBI conditioning + haploidentical alloHSCT alive at 30 days post-transplantation.

    Measured: 30 Days

Secondary outcomes (3)

  1. Rate of neutrophil engraftment at 30 days

    Proportion of patients undergoing BFR-TBI conditioning + haploidentical alloHSCT with neutrophil engraftment at 30 days post-transplantation.

    -Neutrophil engraftment is defined as ANC recovery to >500/uL.

    Measured: 30 days

  2. Rate of platelet recovery at 100 days post-transplantation

    Proportion of patients with platelets > 20/uL with no platelet transfusions within the prior 7 days at day 100 post-transplantation.

    Measured: 100 days

  3. Rate of severe chronic GVHD at 365 days post-transplantation

    Proportion of patients with severe chronic GVHD at day 365 post-transplantation.

    -Severe chronic GVHD is defined by NIH Consensus Criteria for GVHD severity

    Measured: 365 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 May 2018
  2. Study start18 Jul 2018
  3. Primary completion7 Nov 2021
  4. Study completion6 Nov 2024

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03524235
Sponsor's protocol ID
IIT2017-03-Merin-HaploBFR
Status last verified
Nov 2024
First submitted
2 May 2018
Last updated
12 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Total Body Irradiation, Haploidentical Stem Cell Transplantation and CD56-Enriched Donor Lymphocyte Infusion in people with Multiple Myeloma and CLL, run by Noah Merin 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 30 inclusion and 15 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: finished, as of the sponsor's last update on 12 Nov 2024. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Rate of Survival at 30 days post -transplantation (time frame: 30 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03524235.

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 12 Nov 2024.

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