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A Study of TTI-622 in Combination With Daratumumab Hyaluronidase-fihj in People With Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TTI-622
Daratumumab Hyaluronidase-fihj
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring TTI-622, Daratumumab Hyaluronidase-fihj, 21-122

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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:

    1. Serum myeloma (M)-protein greater than or equal to 0.5 g/dL (5 g/L).
    2. Urine M-protein greater or equal to 200 mg/24 h.
    3. Involved light chain (either kappa or lambda) is >10 mg/dL with an abnormal kappa: lambda ratio.
    4. 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.
  • 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:

    1. Absolute neutrophil count (ANC) >1,000/mm^3 (unless myelosuppression is secondary to bone marrow plasmacytosis expressed by >50% of cellularity).
    2. 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)
    3. Hemoglobin ≥8.0 g/dL (transfusion support is not permitted within 7 days of enrollment).
  • Adequate Renal Function defined by:

    a. 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:

    1. 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.
    2. Alkaline phosphatase <2.5 x ULN (<5 x ULN in case of bone metastasis).
    3. 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:

    1. 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.
    2. 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.

Exclusion Criteria:

  • 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).
  • 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.
  • Time between the last doses of previous systemic anti-cancer therapy is less than 5 times the elimination half-life of previous therapy or less than 30 days after last dose of elotuzumab or other Signaling lymphocytic activation molecule F7 (SLAMF7) receptor (also known as anti-CD319) therapy. Recent anti-CD38 therapy is not exclusionary.
  • 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. Patients with a history of cardiac events, and a left ventricular ejection fraction (LVEF) of ≤ 45% at screening will be excluded.
  • 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.

Sites / Locations

  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering MonmouthRecruiting
  • Memorial Sloan Kettering BergenRecruiting
  • Memorial Sloan Kettering CommackRecruiting
  • Memorial Sloan Kettering WestchesterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering NassauRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj

TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall response of TTI-621
measurable disease parameters and International Myeloma Working Group (IMWG) response criteria
Overall response of TTI-622
measurable disease parameters and International Myeloma Working Group (IMWG) response criteria

Full Information

First Posted
October 28, 2021
Last Updated
June 23, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Trillium Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05139225
Brief Title
A Study of TTI-622 in Combination With Daratumumab Hyaluronidase-fihj in People With Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 28, 2021 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Trillium Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
TTI-622, Daratumumab Hyaluronidase-fihj, 21-122

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
A standard 3+3 dose escalation design.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj
Arm Type
Experimental
Arm Description
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.
Arm Title
TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TTI-622
Intervention Description
(-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.
Intervention Type
Drug
Intervention Name(s)
Daratumumab Hyaluronidase-fihj
Intervention Description
Daratumumab hyaluronidase-fihj SC 1800 mg days 1, 8, 15, and 22.
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicities
Description
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.
Time Frame
28-day observation period following C1D1 of therapy
Secondary Outcome Measure Information:
Title
Overall response of TTI-621
Description
measurable disease parameters and International Myeloma Working Group (IMWG) response criteria
Time Frame
2 years
Title
Overall response of TTI-622
Description
measurable disease parameters and International Myeloma Working Group (IMWG) response criteria
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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: a. 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. Exclusion Criteria: 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). 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexander Lesokhin, MD
Phone
646-608-3717
Email
lesokhia@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Caryln Rose Tan, MD
Phone
646-608-3778
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Phone
646-608-3717
First Name & Middle Initial & Last Name & Degree
Neha Korde
Phone
212-639-7664
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Phone
646-608-3717
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Phone
646-608-3717
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Phone
646-608-3717
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Phone
646-608-3717
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Phone
646-608-3717
First Name & Middle Initial & Last Name & Degree
Neha Korde, MD
Phone
212-639-7664
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Lesokhin, MD
Phone
646-608-3717

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

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A Study of TTI-622 in Combination With Daratumumab Hyaluronidase-fihj in People With Multiple Myeloma

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