Allogeneic ORCA-Q Stem Cell Transplant for the Treatment of Relapsed and Refractory High Risk Multiple Myeloma

NCT07759102 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UCDCC330NCI-2026-05456P30CA093373
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the effect of allogeneic Orca-Q stem cell transplant in treating patients with high-risk multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). An allogeneic (donor) transplant uses blood forming stem cells (graft) from a matched donor. When the healthy blood forming (stem) cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease \[GVHD\]). Orca-Q includes some T cells (a type a white blood cell) that are thought to help prevent some of the known complications as well as help attack the cancer cells. However, Orca-Q removes a specific type of T cell called naive T lymphocytes. Naive T cells may contribute to GVHD and are not thought to be required for the success of the treatment. Removing these cells may help reduce the frequency or severity of GVHD. Giving chemotherapy, such as thiotepa, busulfan, and fludarabine, before a donor stem cell transplant helps kill cancer cells in the body and prepare the body to receive the transplant graft. Giving allogeneic Orca-Q may be safe, tolerable, and/or effective in treating patients with relapsed or refractory (R/R) high-risk multiple myeloma.

Conditions

Recurrent Multiple Myeloma; Refractory Multiple Myeloma

Keywords

ORCA-Q

Outcome Measures

Primary Outcomes (1)

• Incidence of primary graft failure without grade II-IV acute graft-versus-host disease (GVHD)

  Frequency and proportions will be obtained.

  From date of transplant and up to 30 days post-transplant

Secondary Outcomes (10)

• Overall survival

  From transplant to death from any cause, assessed up to day 365 post-transplant

• Progression-free survival

  From transplant to progressive disease or death, assessed up to 365 days post-transplant

• Time to relapse

  From transplant to disease progression, initiation of new anti-multiple myeloma treatment, or death, whichever occurs first, assessed up to 365 days post-transplant

• Non-relapse mortality

  From transplant to death from any cause not including disease progression, assessed up to 365 days post-transplant

• Number of treatment-related adverse events (AEs)

  From date of enrollment up to 100 days post-transplant

Study Arms (1)

Treatment (Orca-Q, thiotepa, busulfan, fludarabine)

EXPERIMENTAL

Recipient participants receive thiotepa IV over 3 hours on days -7 and -6, busulfan IV over 3 hours on days -5 to -3, fludarabine IV over 30 minutes on days -5 to -2, Orca-Q prime IV on day 0, followed by Orca-Q supplement IV on day 0 or 1 in the absence of disease progression or unacceptable toxicity.

Biological: Allogeneic Defined Hematopoietic Stem Cells/Immune Cells; Drug: Busulfan; Biological: Filgrastim; Drug: Fludarabine; Drug: Granulocyte Colony-Stimulating Factor; Drug: Thiotepa

Interventions

Allogeneic Defined Hematopoietic Stem Cells/Immune Cells BIOLOGICAL

Given Orca-Q prime IV

Also known as: Allogeneic Defined HSCs/Immune Cells, Allogeneic Defined Stem and Immune Cells, Orca-Q

Treatment (Orca-Q, thiotepa, busulfan, fludarabine)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (Orca-Q, thiotepa, busulfan, fludarabine)

Filgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi, Filgrastim-ayow, Filgrastim-sndz, G-CSF, Granix, Neupogen, Neutroval, Nivestim, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, Releuko, rG-CSF, Tbo-filgrastim, Tevagrastim, XM02, Zarxio

Treatment (Orca-Q, thiotepa, busulfan, fludarabine)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (Orca-Q, thiotepa, busulfan, fludarabine)

Granulocyte Colony-Stimulating Factor DRUG

Given SC

Also known as: Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, GCSF, Granulocyte Colony Stimulating Factor, Pluripoietin

Treatment (Orca-Q, thiotepa, busulfan, fludarabine)

Thiotepa DRUG

Given IV

Also known as: 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa, SH 105, SH-105, SH105, STEPA, Tepadina, Tepylute, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene Thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312

Treatment (Orca-Q, thiotepa, busulfan, fludarabine)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and sign informed consent
• Age ≥ 18 years and ≤ 65 years
• Patients should be in very good partial response (VGPR) (5% or less plasma cells in the marrow) or better response status at the time of stem cell transplant with no evidence of central nervous system (CNS) disease. Patients in complete response (CR) should have minimal residual disease (MRD) positivity
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1; or Karnofsky performance status (KPS) of ≥ 70%
• ≥ 60 days washout period from the last dose of an anti-CD38 antibody before the allogeneic transplant
• ≥ 6 months washout period from the last autologous transplant before the allogeneic transplant
• Related or unrelated donors available as follows:
• Sibling donor who is a 7/8 mismatched or 8/8 matched for human leukocyte antigen (HLA)-A, -B, -C, -DRB1
• Matched unrelated donor who is a 7/8 mismatched or 8/8 matched for HLA-A, -B, -C, and -DRB1
• A diagnosis of relapsed or refractory defined as:
• Primary refractory disease or relapse \< 12 months following initial therapy that includes an immunomodulatory agent, proteasome inhibitor, anti-CD38 monoclonal antibody, and corticosteroid
• Relapse \< 12 months after first autologous stem cell transplant
• Failing to achieve complete response or relapsing after chimeric antigen receptor (CAR)-T treatment or bispecific antibodies; or indicated but ineligible for either bispecific antibodies or CAR-T cells due to low blood counts
• No appropriate standard of care therapy per investigator
• A diagnosis of ultra-high risk multiple myeloma defined as having at least one or more of these criteria:

You may not qualify if:

• Prior allogeneic hematopoietic cell transplantation (HCT)
• Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy), peri-transplant anti-thymocyte globulin (ATG), or alemtuzumab
• Positive anti-donor HLA antibodies against a mismatched allele in the selected donor determined by either:
• A positive crossmatch test of any titer; or
• The presence of anti-donor HLA antibody to any HLA locus
• Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) \> 4
• Uncontrolled bacterial, viral, or fungal infections (currently taking antimicrobial therapy and with no clinical improvement) at time of enrollment
• Seropositive for HIV-1 or -2, human T-cell lymphotropic virus (HTLV)-1 or -2
• Documented allergy or documented hypersensitivity to iron dextran or bovine, murine, algal or Streptomyces avidinii proteins
• Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers or any carcinoma in situ that have been curatively resected
• History of idiopathic or secondary myelofibrosis
• Individuals who are pregnant or breastfeeding
• Any condition that would prohibit the understanding or rendering of informed consent
• Any condition that in the opinion of the investigator would interfere with the subject's safety or compliance while on study
• A diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

Sponsors & Collaborators

• University of California, Davis: lead
• National Cancer Institute (NCI): collaborator
• Orca Biosystems, Inc.: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Busulfan; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine; Thiotepa

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mehrdad Abedi

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Office of Clinical Research

CONTACT

916-382-6970; OCRReferral@health.ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 12, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2032
• Study Completion (Estimated): September 1, 2033
• Last Updated: August 12, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)