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

NCT03524235 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IIT2017-03-Merin-HaploBFR
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Multiple Myeloma; CLL; Chronic Lymphocytic Leukemia; Lymphoma; Hodgkin Lymphoma

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

Outcome Measures

Primary Outcomes (1)

• Rate of Survival at 30 days post -transplantation

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

  30 Days

Secondary Outcomes (3)

• Rate of neutrophil engraftment at 30 days

  30 days

• Rate of platelet recovery at 100 days post-transplantation

  100 days

• Rate of severe chronic GVHD at 365 days post-transplantation

  365 days

Study Arms (2)

Subjects

EXPERIMENTAL

Pre-Transplantation Conditioning (Bendamustine, Fludarabine, and Rituximab + Total Body Irradiation) + Haploidentical Stem Cell Transplantation with CD56-enriched donor lymphocyte infusion

Radiation: Total Body Irradiation; Procedure: Haploidentical Stem Cell Transplantation; Biological: CD56-Enriched Donor Lymphocyte Infusion; Drug: Bendamustine; Drug: Fludarabine; Drug: Rituximab

Controls

NO INTERVENTION

Patients undergoing standard-of-care reduced-intensity peripheral blood allogeneic stem cell transplantation (any indication, donor source, conditioning regimen) using PTCy GVHD prophylaxis.

Interventions

Total Body Irradiation RADIATION

Pre-Transplantation Total Body Irradiation

Also known as: TBI

Subjects

Haploidentical Stem Cell Transplantation PROCEDURE

Haploidentical Stem Cell Transplantation

Subjects

CD56-Enriched Donor Lymphocyte Infusion BIOLOGICAL

CD56-Enriched Donor Lymphocyte Infusion

Subjects

Bendamustine DRUG

Pre-Transplantation Bendamustine

Also known as: Bendeka; Treanda

Subjects

Fludarabine DRUG

Pre-Transplantation Fludarabine

Also known as: Fludara

Subjects

Rituximab DRUG

Pre-Transplantation Rituximab (Rituximab for lymphoma diagnosis only)

Also known as: Rituxan

Subjects

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age 18 - 75 years
• ECOG 0 - 2
• HIV-positive patients are allowed if these criteria are met:
• No history of opportunistic infections
• CD4+ cell count greater or equal to 250 cells/mm3
• No history of non-malignancy AIDS-defining conditions other than historical low CD4+ cell counts
• Patient is on antiretroviral therapy with undetectable viral load. There must be minimal interactions of the antiviral therapy with the experimental treatment (antiretroviral such as ritonavir is potent CYP3A4 inhibitor and p-gp inducer may interact with tacrolimus resulted in increased serum concentration of tacrolimus).
• Patients must have a related donor or who is at minimum HLA haploidentical. The donor and recipient must be identical at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype. An unrelated donor search is not required. (Patients with a readily-available, suitable, fully-matched sibling donor less than age 55 are not eligible for this trial, these patients should proceed to transplant using the matched related donor as standard-of-care).
• Criteria for Donor Eligibility
• Age greater than 12 years
• Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT).
• In the event that two or more eligible donors are identified, the following order of priority will be used to determine the preferred donor:
• Medically and psychologically fit and willing to donate
• For CMV seronegative recipients, a CMV seronegative donor
• Red blood-cell compatibility

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• Noah Merin: lead
• Miltenyi Biomedicine GmbH: collaborator
• Teva Branded Pharmaceutical Products R&D, Inc.: collaborator

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Hodgkin Disease; Neoplasm, Residual

Interventions

Whole-Body Irradiation; Bendamustine Hydrochloride; fludarabine; fludarabine phosphate; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Noah Merin, MD, PhD

  Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute

  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 INVESTIGATOR
• PI Title: Assistant Clinical Professor, Principal Investigator

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: May 14, 2018
• Study Start: July 18, 2018
• Primary Completion: November 7, 2021
• Study Completion: November 6, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Locations

US (1)