NCT03019666

Brief Summary

This is a phase I trial with pilot expansion of HLA-haploidentical or HLA-mismatched related donor nicotinamide expanded-natural killer (NAM-NK) cell based therapy for patients with relapsed or refractory multiple myeloma (MM) or relapsed/refractory CD20-positive non-Hodgkin lymphoma (NHL). The primary endpoint of the study is to determine the maximum tolerated dose (MTD) of NAM-NK cells while maintaining safety.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
39

participants targeted

Target at P50-P75 for phase_1 multiple-myeloma

Timeline
Completed

Started Oct 2017

Typical duration for phase_1 multiple-myeloma

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 11, 2017

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 12, 2017

Completed
9 months until next milestone

Study Start

First participant enrolled

October 18, 2017

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 15, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2022

Completed
Last Updated

November 4, 2022

Status Verified

November 1, 2022

Enrollment Period

4.8 years

First QC Date

January 11, 2017

Last Update Submit

November 2, 2022

Conditions

Multiple MyelomaNon-Hodgkin LymphomaDiffuse Large B Cell LymphomaMantle-Cell LymphomaFollicular LymphomaIndolent B Cell LymphomaPrimary Mediastinal LymphomaLymphoplasmacytic Lymphoma

Keywords

MMNHLNK CellNK Cells

Outcome Measures

Primary Outcomes (2)

  • Occurrence of any grade 4 or greater suspected adverse reaction

    24 hours post infusion

  • Occurrence of Grade III or IV acute graft-versus-host disease (aGVHD)

    28 days post infusion

Secondary Outcomes (3)

  • Occurrence of treatment related mortality (TRM)

    2 months post infusion

  • Occurrence of disease response

    28 days post infusion

  • Number of patients alive without progression

    1 year post infusion

Study Arms (2)

Multiple Myeloma

EXPERIMENTAL

After a lymphodepleting preparative regimen of cyclophosphamide and fludarabine, patients receive expanded NAM-NK cells followed by a short course of interleukin-2 (IL-2) to facilitate natural killer cell survival and expansion in vivo. Monoclonal antibodies and elotuzumab for Multiple Myeloma patients, will be administered prior to and after the natural killer cell infusion(s) to facilitate tumor targeting and antibody dependent cellular cytotoxicity (ADCC).

Biological: Nicotinamide Expanded Haploidentical or Mismatched Related Donor Natural Killer Cells

Non-Hodgkin Lymphoma

EXPERIMENTAL

After a lymphodepleting preparative regimen of cyclophosphamide and fludarabine, patients receive expanded NAM-NK cells followed by a short course of interleukin-2 (IL-2) to facilitate natural killer cell survival and expansion in vivo. Monoclonal antibodies and rituximab for Non-Hodgkin Lymphoma patients, will be administered prior to and after the natural killer cell infusion(s) to facilitate tumor targeting and antibody dependent cellular cytotoxicity (ADCC).

Biological: Nicotinamide Expanded Haploidentical or Mismatched Related Donor Natural Killer Cells

Interventions

Nicotinamide Expanded Haploidentical or Mismatched Related Donor Natural Killer CellsBIOLOGICAL

* Cyclophosphamide 40 mg/kg x 1 day on Day -5 * Fludarabine 25 mg/m\^2 x 3 days (Day -5, Day -4, day-3)

Also known as: NAM-NK
Multiple MyelomaNon-Hodgkin Lymphoma

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥18 to ≤70 years of age
  • Meets one of the following disease criteria:
  • Multiple Myeloma (MM) meeting one of the following:
  • relapsed/refractory disease after two lines of therapies, including a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) and an immunomodulatory drug (thalidomide, lenalidomide or pomalidomide)
  • relapsed disease between 2-18 months of 1st autologous stem cell transplantation,
  • relapsed disease at least 4 months after allogeneic stem cell transplantation with no evidence of active graft versus host disease and no availability of donor lymphocyte infusion
  • measurable disease defined as serum IgG, A, M M-protein ≥ 0.5g/dL or serum IgD M-protein ≥ 0.5 g/dL, or urine M-protein ≥ 200 mg/24 hours
  • at least 4 weeks since plasmapheresis
  • at least 3 days between last corticosteroids and study treatment start
  • CD20-positive B-cell Non-Hodgkin Lymphoma (NHL)
  • CD20 expression confirmed by flow cytometry or immunohistochemistry and meeting one or more of the following:
  • evidence of relapsed/refractory disease that has failed conventional therapy and failed/not eligible/refused studies of a higher priority,
  • relapsed disease at least 60 days after autologous stem cell transplantation
  • relapsed disease at least 4 months after allogeneic stem cell transplantation with no evidence of active graft versus host disease and no availability of donor lymphocyte infusion
  • has measurable disease \>1.5 cm in diameter
  • +13 more criteria

You may not qualify if:

  • Active, untreated CNS involvement
  • Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), or high-grade lymphomas (Burkittt's lymphoma/Lymphoblastic lymphoma)
  • Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. For elotuzumab arm: Women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days of study treatment start (24 hours prior to the start of elotuzumab)
  • Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
  • Class II or greater New York Heart Association Functional Classification criteria (appendix III) or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
  • Active autoimmune disease requiring immunosuppressive therapy
  • History of severe asthma, presently on chronic medications (a history of mild asthma requiring inhaled steroids only is eligible)
  • New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
  • Active uncontrolled bacterial, fungal, or viral infections - all prior infections must have resolved following optimal therapy
  • Known hypersensitivity to any of the study agents used
  • For MM patients only:
  • Prior radiotherapy within 2 weeks prior to the administration of study drug"
  • Surgery within 4 weeks
  • Chemo within 3 weeks (6 weeks for melphalan, or monoclonal antibodies)
  • Received investigational drugs within the 14 days before 1st dose of study drug
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

  • Cichocki F, Zhang B, Wu CY, Chiu E, Day A, O'Connor RS, Yackoubov D, Simantov R, McKenna DH, Cao Q, Defor TE, Janakiram M, Wangen R, Cayci Z, Snyder N, Kumar A, Grzywacz B, Hwang J, Geffen Y, Miller JS, Maakaron J, Bachanova V. Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma. Sci Transl Med. 2023 Jul 19;15(705):eade3341. doi: 10.1126/scitranslmed.ade3341. Epub 2023 Jul 19.

    PMID: 37467318DERIVED

MeSH Terms

Conditions

Multiple MyelomaLymphoma, Non-HodgkinLymphoma, Large B-Cell, DiffuseLymphoma, Mantle-CellLymphoma, FollicularLymphoma, B-Cell, Marginal Zone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesLymphomaLymphatic DiseasesLymphoma, B-Cell

Study Officials

  • Veronika Bachanova, MD, PhD

    University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 11, 2017

First Posted

January 12, 2017

Study Start

October 18, 2017

Primary Completion

August 15, 2022

Study Completion

August 15, 2022

Last Updated

November 4, 2022

Record last verified: 2022-11

Locations

US(1)