Multiple MyelomaPhase 1NCT05139225
A Study of TTI-622 in Combination With Daratumumab Hyaluronidase-fihj in People With Multiple Myeloma
A Phase 1 study testing TTI-622 and Daratumumab Hyaluronidase-fihj in people with Multiple Myeloma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma. The researchers look for the highest dose TTI-622 that causes few or mild side effects in participants when given in combination with daratumumab hyaluronidase-fihj. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- TTI-622 and Daratumumab Hyaluronidase-fihj
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 7 sitesUnited States
- Study dates
- 28 Oct 2021to 1 Jul 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with relapsed or refractory multiple myeloma, as defined by the international myeloma working group (IMWG) updated criteria (Appendix A) who have measurable disease defined by one or more of the following:
- Serum myeloma (M)-protein greater than or equal to 0.5 g/dL (5 g/L).
- Urine M-protein greater or equal to 200 mg/24 h.
- Involved light chain (either kappa or lambda) is >10 mg/dL with an abnormal kappa: lambda ratio.
- A biopsy proven plasmacytoma(s) that is new or definitely increased. Increase is defined as a 50% and at least 1 cm increase as measured serially by the sum of the products of the cross-diameters of the measurable lesion.
- Patients must have received at least 3 prior lines of therapy not having received Daratumumab Hyaluronidase-fihj in the last line of therapy, and have been previously exposed to a proteasome inhibitor, an IMiD and be considered refractory to an FD Aapproved anti-CD38 mAb used either in combination or as a single agent. Refractory is defined as progression on or within 60 days of receiving a treatment program containing an anti-CD38 monoclonal antibody.
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- Female or male patients age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. PS-3 is permitted if PS is due solely to bone pain.
- Adequate hematological function including:
- Absolute neutrophil count (ANC) >1,000/mm^3 (unless myelosuppression is secondary to bone marrow plasmacytosis expressed by >50% of cellularity).
- Platelet count >75,000/mm^3 for the dose finding portion, and > 50,000/ mm^3 for the expansion part.(transfusion is not permitted within 7 days of enrollment)
- Hemoglobin ≥8.0 g/dL (transfusion support is not permitted within 7 days of enrollment).
- Adequate Renal Function defined by:
- Estimated creatinine clearance >30 mL/min as calculated using the CKD-EPI equation. (If an estimated creatinine clearance CrCl is believed to be inaccurate for a patient, 24-hour urine collection with actual assessment of CrCl is allowed)
- Adequate Liver Function, including:
- Aspartate and alanine aminotransferase (AST and ALT) < 2.5 x upper limit of normal (ULN); <5.0 x ULN if there is liver involvement by the tumor.
- Alkaline phosphatase <2.5 x ULN (<5 x ULN in case of bone metastasis).
- Total bilirubin < 2.0 mg/dL, except in patients with Gilbert Syndrome who must have a total bilirubin less than 3.0 mg/dL.
- Seronegative for Hepatitis B surface (HBs) or Hepatitis B core (HBc) antigens. Patients with positive antigens must be tested for hepatitis B virus (HBV) by reverse transcription polymerase chain reaction (RT-PCR). Patients who are HBV RNA negative are eligible.
- Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, patients must be tested for the presence of antigen by RT-PCR. Patients who are hepatitis C virus (HCV) RNA negative with adequate liver function as described above are eligible.
- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤ 1, with the exception of peripheral neuropathy attributable to bortezomib.
- Serum pregnancy test (for females of childbearing potential) negative at screening. Female patients of non-childbearing potential must meet at least 1 of the following criteria:
- Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.
- Have undergone a documented hysterectomy and/or bilateral oophorectomy. Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.
- Signed and dated Informed Consent by study participant and/ or Legally Authorized Representative (LAR).
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
Who cannot join
- Patients with other malignancies in addition to multiple myeloma are not eligible if the other malignancy has required treatment within the past 3 years or is not in complete remission with the exceptions of successfully treated non-metastatic basal cell carcinoma, squamous cell skin carcinoma, or in-situ carcinoma.
- History of active autoimmune disorders (including but not limited to: Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that require systemic therapy, which may compromise or impair the immune system.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Patients with active uncontrolled bacterial, fungal or viral infection, including known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) related illness.
- Major surgery within 4 weeks prior to study entry.
- Radiation therapy within 2 weeks prior to study entry (bone lesions requiring radiation may be treated with limited [i.e., ≤ 25% of bone marrow in field] radiation therapy during this period).
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- Patients with a history of stem cell transplant (autologous or allogeneic) within 100 days prior to study enrollment.
- Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry.
- Therapy with a monoclonal antibody, including but not limited to antiCD38 antibody, elotuzumab, T or NK cell re-directing therapy (ex. bispecific therapy), or antibody-drug conjugate within 30 days of study treatment initiation. Treatment with other anti-multiple myeloma therapies within 14 days of study treatment initiation.
- Patient known to be refractory to platelet or red blood cell transfusions.
- Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF, New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
- Fertile male patients and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
- Other acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Memorial Sloan Kettering Cancer Center
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: A Phase Ib Study Of The Combination Of CD47 Blockade With SIRP-Alpha FC Fusion Proteins (TTI-622) And Daratumumab Hyaluronidase-fihj For Patients With Relapsed or Refractory Multiple Myeloma
This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma. The researchers look for the highest dose TTI-622 that causes few or mild side effects in participants when given in combination with daratumumab hyaluronidase-fihj. Once the researchers find the highest safe dose of each study drug, they will further test the combination TTI-622 + daratumumab hyaluronidase-fihj) in new participants to find out if the combinations are effective in treating relapsed/refractory multiple myeloma. Researchers think that combining TTI-621 or TTI-622 with daratumumab hyaluronidase-fihj, a standard treatment for multiple myeloma, may be an effective treatment approach.
- Conditions
- Multiple Myeloma
- Being tested
- TTI-622, Daratumumab Hyaluronidase-fihj
- Keywords
- TTI-622, Daratumumab Hyaluronidase-fihj, 21-122
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTI-622Drug
(-2) 0.4 mg/kg (-1) 0.8 mg/kg
(1 ) 1.2 mg/kg (2) 2 mg/kg (3) 4 mg/kg (4) 8 mg/kg (5) 12 mg/kg
The appropriate dose of TTI-622 will be administered IV over 60 minutes, however, can be extended up to 4 hours to mitigate Infusion-related reactions.
Daratumumab Hyaluronidase-fihjDrug
Daratumumab hyaluronidase-fihj SC 1800 mg days 1, 8, 15, and 22.
| Study group | Role | What they receive |
|---|---|---|
| TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj | Experimental | TTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter. Receives: Drug: TTI-622; Drug: Daratumumab Hyaluronidase-fihj |
| TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj | Experimental | TTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter. Receives: Drug: TTI-622; Drug: Daratumumab Hyaluronidase-fihj |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities
Dose limiting toxicities are defined as any of the following treatment emergent adverse events that occur during the 28-day DLT observation period, inclusive of pre-dose testing on C2D1. Adverse events for which a relationship to study treatment cannot be ruled out should be considered possibly related to treatment. Toxicity grading will be adjudicated according to NCI CTCAE version 5.
Measured: 28-day observation period following C1D1 of therapy
Secondary outcomes (2)
Overall response of TTI-621
measurable disease parameters and International Myeloma Working Group (IMWG) response criteria
Measured: 2 years
Overall response of TTI-622
measurable disease parameters and International Myeloma Working Group (IMWG) response criteria
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start28 Oct 2021
- Primary completion1 Jul 2026
- Study completion1 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- A standard 3+3 dose escalation design.
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Trillium Therapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Alexander Lesokhin, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05139225
- Sponsor's protocol ID
- 21-122
- Status last verified
- Jul 2026
- First submitted
- 28 Oct 2021
- Last updated
- 6 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study Of The Combination Of CD47 Blockade With SIRP-Alpha FC Fusion Proteins (TTI-622) And Daratumumab Hyaluronidase-fihj For Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT05139225
- Acronym / sponsor ID
- 21-122
- Conditions
- Multiple Myeloma
- Keywords
- TTI-622, Daratumumab Hyaluronidase-fihj, 21-122
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Trillium Therapeutics Inc.
- Study start
- 28 Oct 2021 (actual)
- Primary completion
- 1 Jul 2026 (actual)
- Study completion
- 1 Jul 2026 (actual)
- First posted
- 1 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma. The researchers look for the highest dose TTI-622 that causes few or mild side effects in participants when given in combination with daratumumab hyaluronidase-fihj. Once the researchers find the highest safe dose of each study drug, they will further test the combination TTI-622 + daratumumab hyaluronidase-fihj) in new participants to find out if the combinations are effective in treating relapsed/refractory multiple myeloma. Researchers think that combining TTI-621 or TTI-622 with daratumumab hyaluronidase-fihj, a standard treatment for multiple myeloma, may be an effective treatment approach.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A standard 3+3 dose escalation design.
| Arm | Type | Receives |
|---|---|---|
| TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj | Experimental | Drug: TTI-622, Drug: Daratumumab Hyaluronidase-fihjTTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter. |
| TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj | Experimental | Drug: TTI-622, Drug: Daratumumab Hyaluronidase-fihjTTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Patients with relapsed or refractory multiple myeloma, as defined by the international myeloma working group (IMWG) updated criteria (Appendix A) who have measurable disease defined by one or more of the following:
- Patients must have received at least 3 prior lines of therapy not having received Daratumumab Hyaluronidase-fihj in the last line of therapy, and have been previously exposed to a proteasome inhibitor, an IMiD and be considered refractory to an FD Aapproved anti-CD38 mAb used either in combination or as a single agent. Refractory is defined as progression on or within 60 days of receiving a treatment program containing an anti-CD38 monoclonal antibody.
- Female or male patients age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. PS-3 is permitted if PS is due solely to bone pain.
- Adequate hematological function including:
Key exclusion criteria (13 listed)
- Patients with other malignancies in addition to multiple myeloma are not eligible if the other malignancy has required treatment within the past 3 years or is not in complete remission with the exceptions of successfully treated non-metastatic basal cell carcinoma, squamous cell skin carcinoma, or in-situ carcinoma.
- History of active autoimmune disorders (including but not limited to: Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that require systemic therapy, which may compromise or impair the immune system.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Patients with active uncontrolled bacterial, fungal or viral infection, including known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) related illness.
- Major surgery within 4 weeks prior to study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TTI-622(-2) 0.4 mg/kg (-1) 0.8 mg/kg (1 ) 1.2 mg/kg (2) 2 mg/kg (3) 4 mg/kg (4) 8 mg/kg (5) 12 mg/kg The appropriate dose of TTI-622 will be administered IV over 60 minutes, however, can be extended up to 4 hours to mitigate Infusion-related reactions. | Drug | TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj, TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj |
| Daratumumab Hyaluronidase-fihjDaratumumab hyaluronidase-fihj SC 1800 mg days 1, 8, 15, and 22. | Drug | TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj, TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj |
Primary outcome
Incidence of dose-limiting toxicities
Time frame: 28-day observation period following C1D1 of therapy
Dose limiting toxicities are defined as any of the following treatment emergent adverse events that occur during the 28-day DLT observation period, inclusive of pre-dose testing on C2D1. Adverse events for which a relationship to study treatment cannot be ruled out should be considered possibly related to treatment. Toxicity grading will be adjudicated according to NCI CTCAE version 5.
2 secondary outcomes
Overall response of TTI-621
Time frame: 2 years
Overall response of TTI-622
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander Lesokhin, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TTI-622 and Daratumumab Hyaluronidase-fihj in people with Multiple Myeloma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (time frame: 28-day observation period following C1D1 of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.