- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04499339
A Phase I/IIa Clinical Trial to Assess Feasibility, Safety and Antitumor Activity of Autologous SLAMF7 CAR-T Cells in Multiple Myeloma
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in-human clinical trial of adoptive immunotherapy with autologous signaling lymphocytic activation molecule F7 (SLAMF7) chimeric antigen receptor (CAR)-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in human clinical trial of adoptive immunotherapy with autologous SLAMF7 CAR-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
SLAMF7 CAR-T cells are manufactured using virus-free gene-transfer using the Sleeping Beauty transposon system.
The CAR-T cell product is formulated to contain equal proportions of CD8 cytotoxic and CD4 helper SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Prof. Michael Hudecek
- Phone Number: +49 931 20140001
- Email: hudecek_m@ukw.de
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Signed informed consent form.
- Patient is ≥18 years of age.
- Patient is willing and able to adhere to the protocol requirements.
Patient with diagnosis of MM who has been treated with at least 2 prior lines of treatment, including at least one cycle of high-dose chemotherapy with autologous hematopoietic stem cell transplantation if the patient was eligible, and exposure to an immunomodulatory imide drug (e.g. lenalidomide and/or pomalidomide), a proteasome inhibitor, and an anti-CD38 antibody.
(Note: Induction therapy, up to 2 cycles of high-dose chemotherapy with autologous hematopoietic stem cell transplantation, and subsequent consolidation and/or maintenance therapy are considered one line of treatment).
At least one of the following subcriteria must be measured in the patient:
- Serum M-protein greater or equal to 0.5 g/dL
- Urine M-protein greater or equal to 200 mg/24 h
- Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal
- A biopsy-proven evaluable plasmacytoma
- Bone marrow plasma cells >10% of total bone marrow cells (>30% if bone marrow plasma cells are the only marker of measurable disease)
- Patients previously treated with an anti-SLAMF7 antibody are eligible.
- Karnofsky performance status ≥60%. If patient has a Karnofsky performance status <60% (e.g. after a spinal cord injury) but is judged to be medically fit by the investigator, patient is eligible.
Female patients of childbearing potential must:
- have a negative pregnancy test (blood) at screening.
- either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption, from screening through 1 year following the investigantional medicinal product (IMP) infusion. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) must be practiced. The patient should be informed of the potential risks associated with becoming pregnant while enrolled in this clinical trial. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled.
- Agree to abstain from breast feeding during the study participation and for 1 year after the IMP infusion.
- Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after IMP infusion, even if he has undergone a successful vasectomy.
Exclusion Criteria:
- Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤12 months prior to leukapheresis.
- Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning >12 months, and suffers on chronic Graft-versus-Host Disease and/or is on systemic immune-suppressants.
Patient with diagnosis of MM
- in first relapse following an autologous stem cell transplantation or
- in second relapse that subsequently achieves a complete response that is considered being a candidate for an allogeneic stem cell transplantation, unless the patient explicitly denies undergoing an allogeneic stem cell transplantation.
- Patient has received anti-CD38 and/or anti-SLAMF7 antibodies ≤8 weeks prior to leukapheresis.
Ongoing treatment with systemic immune-suppressants (e.g. systemic cyclosporine or systemic steroids at any dose).
(Note: Physiologic steroid replacement therapy, topical immune-suppressants as e.g. cyclosporine/tacrolimus eye drops and topical steroids are permitted.)
- Echocardiogram with left ventricular ejection fraction <45%.
- Inadequate renal function defined by creatinine clearance (CrCl) ≤45 mL/min using Cockcroft-Gault equation.
- Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN) and total bilirubin >1.5 x ULN (unless due to Gilbert's syndrome and direct bilirubin is ≤1.5 x ULN; unless due to intrahepatic myeloma lesions as demonstrated by MRI or positron emission tomography (PET)/computed tomography (CT) not older than 4 weeks prior to screening).
- International ratio (INR) or partial thromboplastin time (PTT) >1.5 x ULN, unless on a stable dose of anti-coagulant.
- Evidence of human immunodeficiency virus (HIV) infection.
Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV), excluding
- Patients who are hepatitis B surface antigen negative and HBV viral DNA negative
- Patients who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months
- Patients who are seropositive because of hepatitis B virus vaccine
- Patients with known HBV infection but undetectable HBV viral load and on anti-viral therapy to prevent HBV reactivation.
Seropositive for and with active viral infection with hepatitis C virus (HCV), excluding
- Patients who had hepatitis C but had received an antiviral treatment and show no detectable HCV viral RNA for 6 months.
Seropositive for syphilis on treponema pallidum hemagglutination test, excluding
- Patients with negative treponema pallidum antibody absorption test result
- Patients with active infection (e.g. asymptomatic and symptomatic severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) or other serious medical or psychiatric disorder on investigators decision.
- Pregnant or lactating women.
- Current or previous (within 30 days of enrollment) treatment with another IMP.
- Known abuse of alcohol, drugs, or medicinal products.
- Employees of the sponsor, or employees or relatives of the investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: All eligible patients
|
Single infusion of autologous SLAMF7 CAR-T cells
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety determination of the treatment with SLAMF7 CAR-T in phase I
Time Frame: through study completion, an average of 2 years
|
Type, frequency and severity of AEs in phase I
|
through study completion, an average of 2 years
|
Determination of the maximum tolerated dose (MTD) and the recommended phase IIa dose of SLAMF7 CAR-T in patients with MM
Time Frame: through study Phase I completion, an average of 2 years
|
For the primary endpoint in phase I, the maximum tolerated dose will be determined and recommended for phase IIa.
|
through study Phase I completion, an average of 2 years
|
Safety determination of the treatment with SLAMF7 CAR-T in phases I and IIa
Time Frame: through study completion, an average of 2 years
|
Type, frequency and severity of AEs in phase I and IIa
|
through study completion, an average of 2 years
|
Evaluation of the efficacy, defined as overall response rate (ORR) after treatment with SLAMF7 CAR-T in patients with MM
Time Frame: through study completion, an average of 2 years
|
In Phase IIa the efficacy will be evaluated, defined as ORR.
|
through study completion, an average of 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Prof. Michael Hudecek, University Hospital Wuerzburg
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
Other Study ID Numbers
- CARAMBA-1
- 2019-001264-30 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Multiple Myeloma
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Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
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Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on SLAMF7 CAR-T
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Hebei Senlang Biotechnology Inc., Ltd.RecruitingLymphoma | Multiple Myeloma | Acute Lymphoblastic LeukemiaChina
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Nexcella Inc.Not yet recruitingLight Chain (AL) AmyloidosisUnited States
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Bellicum PharmaceuticalsSuspendedHER2-positive Breast Cancer | HER2-positive Gastric Cancer | Solid Tumor, Adult | HER-2 Gene Amplification | HER-2 Protein OverexpressionUnited States
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Southwest Hospital, ChinaUnknownLymphoma, Large B-Cell, DiffuseChina
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Chunrui LiNanjing IASO Biotechnology Co., LtdRecruitingPlasma Cell Leukemia | Relapsed/Refractory Multiple MyelomaChina
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Medical College of WisconsinChildren's Hospital and Health System Foundation, WisconsinCompletedLymphoma, B-Cell | Lymphoma, Non-Hodgkin | Chronic Lymphocytic Leukemia | Small Lymphocytic LymphomaUnited States
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Fuda Cancer Hospital, GuangzhouWithdrawnCAR-T Cell Immunotherapy | Glioma of Brain
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Wuhan Sian Medical Technology Co., LtdWuhan Union Hospital, China; Xiangyang Central Hospital; Jingzhou Central Hospital and other collaboratorsUnknownB Cell Lymphoma | Acute Lymphoblastic LeukemiaChina
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Medical College of WisconsinChildren's Hospital and Health System Foundation, WisconsinRecruitingAcute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Acute Lymphoblastic Leukemia Recurrent | Acute Lymphoblastic Leukemia With Failed Remission | Acute Lymphoblastic Leukemia Not Having Achieved RemissionUnited States
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Zhejiang UniversityYake Biotechnology Ltd.RecruitingMultiple Myeloma | New Diagnosis TumorChina