Recurrent Multiple MyelomaPhase 1NCT07759102

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

A Phase 1 study testing Allogeneic Defined Hematopoietic Stem Cells/Immune Cells, Busulfan and Filgrastim in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by University of California, Davis at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Recurrent Multiple Myeloma, Refractory Multiple Myeloma
What is being tested?: Allogeneic Defined Hematopoietic Stem Cells/Immune Cells, Busulfan and Filgrastim
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUnited States
Study dates: 1 Sep 2026to 1 Sep 2033
Phase: Phase 1

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 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

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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)

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Office of Clinical Research contact

916-382-6970

OCRReferral@health.ucdavis.edu

United States1 site

University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Office of Clinical Research, 916-382-6970, OCRReferral@health.ucdavis.edu
Mehrdad Abedi, MD

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

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:

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.

Conditions: Recurrent Multiple Myeloma, Refractory Multiple Myeloma
Being tested: Allogeneic Defined Hematopoietic Stem Cells/Immune Cells, Busulfan, Filgrastim, Fludarabine, Granulocyte Colony-Stimulating Factor
Keywords: ORCA-Q
Medical subject headings: Multiple Myeloma

What participants receive

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

Allogeneic Defined Hematopoietic Stem Cells/Immune CellsBiological
Also called Allogeneic Defined HSCs/Immune Cells, Allogeneic Defined Stem and Immune Cells, Orca-Q
Given Orca-Q prime IV
Allogeneic Defined Hematopoietic Stem Cells/Immune CellsBiological
Also called Allogeneic Defined HSCs/Immune Cells, Allogeneic Defined Stem and Immune Cells, Orca-Q
Given Orca-Q supplement IV
BusulfanDrug
Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam
Given IV
FilgrastimBiological
Also called Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi
Given SC
FludarabineDrug
Also called Fluradosa
Given IV
Granulocyte Colony-Stimulating FactorDrug
Also called Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3
Given SC
ThiotepaDrug
Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa
Given IV

Study groups in NCT07759102
Study group	Role	What they receive
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. Receives: Biological: Allogeneic Defined Hematopoietic Stem Cells/Immune Cells; Drug: Busulfan; Biological: Filgrastim; Drug: Fludarabine; Drug: Granulocyte Colony-Stimulating Factor; Drug: Thiotepa

What is being measured

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

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

Secondary outcomes (10)

Overall survival
The Kaplan-Meier (KM) method will be used to estimate the median and percentiles for time-to-event endpoints with 95% confidence intervals (CIs).
Measured: From transplant to death from any cause, assessed up to day 365 post-transplant
Progression-free survival
The KM method will be used to estimate the median and percentiles for time-to-event endpoints with 95% CIs.
Measured: From transplant to progressive disease or death, assessed up to 365 days post-transplant
Time to relapse
Measured: 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
Will be analyzed using the cumulative incidence function to account for the competing risk of disease relapse/progression.
Measured: 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)
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.
Measured: From date of enrollment up to 100 days post-transplant
Occurrence of grade 3 or 4 treatment-emergent AEs
Will be classified by severity and graded according to the NCI CTCAE v 6.0. Frequency and proportions will be obtained.
Measured: From date of transplant up to 100 days post-transplant
Incidence of acute GVHD
Measured: From date of transplant up to 100 days post-transplant
Incidence of chronic GVHD
Measured: From date of transplant up to 100 days post-transplant
Incidence of GVHD free, relapse free survival
The KM method will be used to estimate the median and percentiles for time-to-event endpoints with 95% CIs.
Measured: From date of transplant up to 365 days post-transplant
Secondary graft failure rate
Measured: Up to day 365 post-transplant

Timeline

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

1 Sep 20261 Sep 2033

First posted12 Aug 2026
Study start1 Sep 2026 (estimated)
Primary completion1 Sep 2032 (estimated)
Study completion1 Sep 2033 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Recurrent Multiple MyelomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07759102
Sponsor's protocol ID: UCDCC330
Other IDs: NCI-2026-05456, UCDCC330, P30CA093373
Status last verified: Aug 2026
First submitted: 5 Aug 2026
Last updated: 12 Aug 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No