FDA Lifts Clinical Hold on MELANI-01 Trial With CAR T Product UCARTCS1 in Myeloma

November 18, 2020 - The FDA has decided to lift the clinical hold placed on the phase 1 MELANI-01 trial, which is examining the CAR T-cell therapy UCARTCS1 as a treatment for patients with relapsed/refractory multiple myeloma.

The FDA has decided to lift the clinical hold placed on the phase 1 MELANI-01 trial (NCT04142619), which is examining the CAR T-cell therapy UCARTCS1 as a treatment for patients with relapsed/refractory multiple myeloma, according to Cellectis, the manufacturer of the product.1

The company reported that they worked closely with the FDA over the past months since the hold had been put in place to address requests that the regulatory agency had made, which included adjustments to the trial protocol to improve the safety of patients enrolled.

Moreover, Cellectis announced that they will continue to work with the clinical staff on the trial sites, as well as the investigators, to acquire the local approvals needed to reopen the trial and continue to enroll patients.

“We remain confident in the potential clinical benefit of UCARTCS1 product candidate for patients with relapsed/refractory multiple myeloma, a widely unmet need that Cellectis will continue to address,” Carrie Brownstein, MD, chief medical officer of Cellectis, stated in a press release. “The safety of patients enrolled in our clinical trials remains our priority, and we are committed to resuming the clinical development of this promising program.”

The FDA had implemented the clinical hold on MELANI-01in July 2020 after the submission of a safety report on 1 patient with relapsed/refractory disease who was enrolled on the trial and had received the product at dose level 2.2 The patient had received previous treatment with several lines of therapy, including autologous CAR T cells, and after receiving treatment with UCARTCS1, had experienced fatal cardiac arrest; this was found to be a treatment-emergent toxicity. The case was examined, with data collected on both the immediate and underlying causes of this effect.

Before the hold was initiated, Cellectis had expanded patient enrollment at dose level 1. The company had determined that this dose level might be the appropriate choice for further evaluation in the expansion portion of the trial, as well as the recommended dose for the phase 2 trial of the product. This hypothesis was based on an assessment of preliminary clinical and translational findings.

In January 2019, the investigational new drug application to launch MELANI-01 to examine UCARTCS1 product was approved by the FDA. In the open-label, dose-escalation, phase 1 trial, investigators are evaluating the safety and efficacy of 1 infusion of the CS1-targeted CAR T-cell product in patients with relapsed/refractory myeloma;3 they also wanted to identify the maximum-tolerated dose of the allogeneic, off-the-shelf, gene-edited T-cell product.4

The primary objective is to evaluate safety, which includes evaluating the incidence, nature, and severity of toxicities and serious adverse effects experienced with the therapy throughout the trial. To be eligible for enrollment, patients had to have. A confirmed diagnosis of multiple myeloma and have relapsed on previous therapy; they also needed to have an ECOG performance status of 0-1 and acceptable organ function. Patients could not have received previous treatment with an experimental gene therapy targeted toward CS1 or a CS1-targeted CAR T-cell product.

The trial was initiated under the guidance of Krina K. Patel, MD, MSc, who served as the principal investigator and study coordinator, and is also an assistant professor in the Department of Lymphoma/Myeloma of the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center.

David Siegel, MD, who is the director of the Multiple Myeloma Institute at John Theurer Cancer Center, is leading the effort at Hackensack Meridian, and Andrew Rossi, MD, associate clinical director of the Myeloma Center and assistant professor of medicine in the Division of Hematology and Medical Oncology is supervising the site at Weill Cornell Medicine.

Enrollment for 2 other phase 1 dose-escalation trials is ongoing. The AMELI-01 trial (NCT03190278) is examining UCART123 in patients with relapsed and refractory acute myeloid leukemia, while the BALLI-01 trial (NCT04150497) is investigating the use of UCART22 in patients with relapsed and refractory B-cell acute lymphoblastic leukemia.


1. FDA lifts clinical hold on MELANI-01 study evaluating Cellectis’ product candidate UCARTCS1 in multiple myeloma. News release. Cellectis. November 17, 2020. Accessed November 18, 2020. https://bit.ly/36JOOjz.

2. Cellectis reports clinical hold placed on MELANI-01 study. News release. Cellectis. July 6, 2020. Accessed November 18, 2020. https://bit.ly/3f5Ov5C.

3. Study evaluating safety and efficacy of UCART targeting CS1 in patients with relapsed/refractory multiple myeloma (MELANI-01). ClinicalTrials.gov. Updated March 3, 2020. Accessed July 6, 2020. https://clinicaltrials.gov/ct2/show/NCT04142619.

4. Universal chimeric antigen receptors. Cellectis. Accessed November 18, 2020. bit.ly/3gD3Evg.