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

August 5, 2026 updated by: University of California, Davis

A Phase I Study to Evaluate the Safety and Efficacy of ORCA-Q Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Relapsed/ Refractory High Risk Multiple Myeloma

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the safety of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features.

II. To further evaluate the safety of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features.

EXPLORATORY OBJECTIVE:

I. To further evaluate the efficacy of allogeneic ORCA-Q transplantation in subjects with R/R multiple myeloma with high-risk features.

OUTLINE:

DONORS: Donors receive granulocyte colony-stimulating factor (G-CSF) or filgrastim subcutaneously (SC) daily (QD) on days -6 to -3 and undergo apheresis on day -2 or -1. Donors may also undergo a second apheresis on day -1 or 0. Additionally, donors undergo blood sample collection at screening.

PATIENTS: Patients receive thiotepa intravenously (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. Additionally, patients undergo echocardiography or multigated acquisition scan (MUGA) and optional positron emission tomography (PET)/computed tomography (CT) or CT at screening and urine and blood sample collection, as well as bone marrow aspiration and biopsy throughout the study.

After completion of study treatment, patients are followed up on days 1-7, 14, 21, 30, 60, 90, 180, and 365.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
        • Principal Investigator:
          • Mehrdad Abedi, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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:

    • Biallelic TP53 inactivation
    • ≥ 2 HRCAs: del(17p), TP53 mutation, t(4;14), t(14;16), t(14;20), gain(1q), amp(1q), del(1p32)
    • Biallelic del(1p32)
    • High-risk gene expression profile signature
    • Extramedullary disease excluding intramedullary plasmacytoma with extraosseous extension and active CNS disease
    • ≥ 2% circulating plasma cells
  • Creatinine clearance of ≥ 50 mL/min as estimated by Cockcroft-Gault
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) except in subjects with Gilbert's syndrome in whom total bilirubin ≤ 3 times ULN
  • Alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) and aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) ≤ 3 x the upper limit of normal (ULN) or ≤ 5 x ULN if documented liver involvement by disease
  • Estimated glomerular filtration rate (eGFR) > 50mL/minute. Creatinine clearance of ≥ 30 mL/min is allowed in patients eligible for no tacrolimus immunosuppression
  • Pulmonary function as defined by diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
  • Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram, or radionuclide scan (multigated acquisition scan [MUGA])
  • Corrected diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
  • Individuals of childbearing potential or those with partners of childbearing potential must agree to use methods of contraception for the duration of study participation or be surgically sterilized
  • Stated ability and willingness to adhere to the study visit schedule and protocol requirements
  • DONOR: Ability to understand and sign informed consent
  • DONOR: Age ≥ 16 and ≤ 35 years at time of enrollment for unrelated donors and Age ≥ 16 and ≤ 50 years for related donors

  • DONOR: Either one of the following scenarios:

    • Sibling donor who is a 7/8 mismatched or 8/8 matched for HLA-A, -B, -C, and -DRB1, all typed using deoxyribonucleic acid (DNA)-based high-resolution methods
    • Unrelated donor who is 7/8 mismatched or 8/8 matched HLA-A, -B, -C, and -DRB1, all typed using DNA-based high-resolution methods
  • DONOR: Willing to donate stem cell mobilized mononuclear cells for up to two consecutive days
  • DONOR: Able to donate within the continental United States at a site that will employ a Spectra Optia Apheresis System for post-mobilization apheresis
  • DONOR: Meets federal eligibility criteria for donors of viable, leukocyte-rich cells or tissues and all relevant Food and Drug Administration (FDA) Guidance for Industry (Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products, 2007; Use of Donor Screening Tests to Test Donors of Human Cells, Tissues and Cellular and Tissue-Based Products for Infection with Treponema pallidum [syphilis], 2015; Use of Nucleic Acid Tests to Reduce the Risk of Transmission of Hepatitis B Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products, 2016; Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Living Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products [HCT/Ps], 2016)

  • DONOR: Donors determined to be ineligible, based on the results of required testing and/or screening, may nonetheless be included if either applies:

    • The donor is a first-degree blood relative of the recipient
    • Urgent medical need, meaning no comparable human cell product is available, and the recipient is likely to suffer death or serious morbidity without the human cell product, as attested by the investigator
    • Meets any other criteria for donation as specified by standard National Marrow Donor Program (NMDP) guidelines (NMDP donors) or institutional standards (non-NMDP donors)

Exclusion Criteria:

  • 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
  • DONOR: Evidence of uncontrolled, active infection
  • DONOR: Seropositive for HIV-1 or -2, HTLV-1 or -2
  • DONOR: Positive for hepatitis B (HBV) surface antigen (HBsAg), total anti-hepatitis B core antibody (HBcAb, immunoglobulin [I]gG and IgM), HBV nucleic acid testing (NAT), anti-hepatitis C (HCV) antibody, or HCV NAT
  • DONOR: Aberrant CD45RA isoform expression
  • DONOR: Women who are pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (Orca-Q, thiotepa, busulfan, fludarabine)
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.
Drug: Fludarabine
Given IV
Other Names:
  • Fluradosa
Biological: Filgrastim
Given SC
Other Names:
  • G-CSF
  • r-metHuG-CSF
  • Neupogen
  • Filgrastim-aafi
  • Nivestym
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim
  • Filgrastim Biosimilar Filgrastim-sndz
  • Zarxio
  • Filgrastim XM02
  • Tbo-filgrastim
  • Granix
  • Nivestim
  • XM02
  • Filgrastim-sndz
  • Filgrastim Biosimilar Tbo-filgrastim
  • Filgrastim-ayow
  • Releuko
  • Neutroval
Drug: Busulfan
Given IV
Other Names:
  • Busulfex
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
  • 1, 4-Bis[methanesulfonoxy]butane
  • BUS
  • Bussulfam
  • Busulfanum
  • Busulphan
  • CB 2041
  • CB-2041
  • Glyzophrol
  • GT 41
  • GT-41
  • Joacamine
  • Methanesulfonic Acid Tetramethylene Ester
  • Methanesulfonic acid, tetramethylene ester
  • Mielucin
  • Misulban
  • Myeleukon
  • Mylecytan
  • Myleran
  • Sulfabutin
  • Tetramethylene Bis(methanesulfonate)
  • Tetramethylene bis[methanesulfonate]
  • WR-19508
  • Busilvex
Drug: Thiotepa
Given IV
Other Names:
  • Tepadina
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
  • 1,1',1''-Phosphinothioylidynetrisaziridine
  • Girostan
  • N,N', N''-Triethylenethiophosphoramide
  • Tespamine
  • Thio-Tepa
  • Thiofosfamide
  • Thiofozil
  • Thiophosphamide
  • Thiophosphoramide
  • Thiotef
  • Tifosyl
  • TIO TEF
  • Tio-tef
  • Triethylene Thiophosphoramide
  • Triethylenethiophosphoramide
  • Tris(1-aziridinyl)phosphine sulfide
  • WR 45312
  • Thiophosphoamide
  • SH 105
  • SH-105
  • SH105
  • Tepylute
Drug: Granulocyte Colony-Stimulating Factor
Given SC
Other Names:
  • G-CSF
  • Granulocyte Colony Stimulating Factor
  • GCSF
  • Colony Stimulating Factor 3
  • Colony-Stimulating Factor (Granulocyte)
  • Colony-Stimulating Factor 3
  • CSF3
  • G CSF
  • Pluripoietin
Biological: Allogeneic Defined Hematopoietic Stem Cells/Immune Cells
Given Orca-Q prime IV
Other Names:
  • Allogeneic Defined HSCs/Immune Cells
  • Allogeneic Defined Stem and Immune Cells
  • Orca-Q
Biological: Allogeneic Defined Hematopoietic Stem Cells/Immune Cells
Given Orca-Q supplement IV
Other Names:
  • Allogeneic Defined HSCs/Immune Cells
  • Allogeneic Defined Stem and Immune Cells
  • Orca-Q

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of primary graft failure without grade II-IV acute graft-versus-host disease (GVHD)
Time Frame: From date of transplant and up to 30 days post-transplant
Frequency and proportions will be obtained.
From date of transplant and up to 30 days post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From transplant to death from any cause, assessed up to day 365 post-transplant
The Kaplan-Meier (KM) method will be used to estimate the median and percentiles for time-to-event endpoints with 95% confidence intervals (CIs).
From transplant to death from any cause, assessed up to day 365 post-transplant
Progression-free survival
Time Frame: From transplant to progressive disease or death, assessed up to 365 days post-transplant
The KM method will be used to estimate the median and percentiles for time-to-event endpoints with 95% CIs.
From transplant to progressive disease or death, assessed up to 365 days post-transplant
Time to relapse
Time Frame: From transplant to disease progression, initiation of new anti-multiple myeloma treatment, or death, whichever occurs first, assessed up to 365 days post-transplant
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
Time Frame: From transplant to death from any cause not including disease progression, assessed up to 365 days post-transplant
Will be analyzed using the cumulative incidence function to account for the competing risk of disease relapse/progression.
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)
Time Frame: From date of enrollment up to 100 days post-transplant
Will be classified by severity and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 6.0. Frequency and proportions will be obtained.
From date of enrollment up to 100 days post-transplant
Occurrence of grade 3 or 4 treatment-emergent AEs
Time Frame: From date of transplant up to 100 days post-transplant
Will be classified by severity and graded according to the NCI CTCAE v 6.0. Frequency and proportions will be obtained.
From date of transplant up to 100 days post-transplant
Incidence of acute GVHD
Time Frame: From date of transplant up to 100 days post-transplant
From date of transplant up to 100 days post-transplant
Incidence of chronic GVHD
Time Frame: From date of transplant up to 100 days post-transplant
From date of transplant up to 100 days post-transplant
Incidence of GVHD free, relapse free survival
Time Frame: From date of transplant up to 365 days post-transplant
The KM method will be used to estimate the median and percentiles for time-to-event endpoints with 95% CIs.
From date of transplant up to 365 days post-transplant
Secondary graft failure rate
Time Frame: Up to day 365 post-transplant
Up to day 365 post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Davis

Collaborators

National Cancer Institute (NCI)
Orca Biosystems, Inc.

Investigators

  • Principal Investigator: Mehrdad Abedi, University of California, Davis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

September 1, 2032

Study Completion (Estimated)

September 1, 2033

Study Registration Dates

First Submitted

August 5, 2026

First Submitted That Met QC Criteria

August 5, 2026

First Posted (Actual)

August 12, 2026

Study Record Updates

Last Update Posted (Actual)

August 12, 2026

Last Update Submitted That Met QC Criteria

August 5, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCDCC330 (Other Identifier: University of California Davis Comprehensive Cancer Center)
  • P30CA093373 (U.S. NIH Grant/Contract)
  • NCI-2026-05456 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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