A Phase I/IIa Clinical Trial to Assess Feasibility, Safety and Antitumor Activity of Autologous SLAMF7 CAR-T Cells in Multiple Myeloma

NCT04499339 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: CARAMBA-12019-001264-30
• Study Type: interventional
• Target: 38
• Locations: 3 countries
• Sites: 3

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

SLAMF7; Chimeric antigen receptor; CAR; CAR-T cell; immunotherapy; virus-free gene transfer

Outcome Measures

Primary Outcomes (4)

• Safety determination of the treatment with SLAMF7 CAR-T in phase I

  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

  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

  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

  In Phase IIa the efficacy will be evaluated, defined as ORR.

  through study completion, an average of 2 years

Study Arms (1)

All eligible patients

EXPERIMENTAL

Drug: SLAMF7 CAR-T

Interventions

SLAMF7 CAR-T DRUG

Single infusion of autologous SLAMF7 CAR-T cells

All eligible patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Wuerzburg University Hospital: lead
• European Union: collaborator

Study Sites (3)

Centre Hospitalier Universitaire de Lille

Lille, 59037, France

Location

Early Clinical Trial Unit University Hospital Wuerzburg

Würzburg, 97080, Germany

Location

Clinical Trials Unit, Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Related Links

• CARAMBA project homepage

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Prof. Michael Hudecek

  University Hospital Wuerzburg

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: August 5, 2020
• Study Start: July 22, 2020
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

DE (1); FR (1); ES (1)