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NCT04097301

Study of CAR T-cell Therapy in Acute Myeloid Leukemia and Multiple Myeloma

Terminated Phase 1, PHASE2 Results posted Last updated 19 January 2022
What this trial tests

Phase 1, PHASE2 trial testing MLM-CAR44.1 T-cells at day 0 Single intravenous infusion in Acute Myeloid Leukemia in 8 participants. Terminated before completion.

Timeline
27 August 2019
Primary endpoint
18 June 2021
18 June 2021

Quick facts

Lead sponsorAGC Biologics S.p.A.
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment8
Start date27 August 2019
Primary completion18 June 2021
Estimated completion18 June 2021
Sites3 locations across Italy, Czechia

Drugs / interventions tested

Conditions studied

Sponsor

AGC Biologics S.p.A. — full company profile →

Who can join

Adults 1 to 75, any sex, with Acute Myeloid Leukemia or Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase I: Overall Safety of Treatment With MLM-CAR44.1 T-cells Primary · For 30 days following CAR T-cell infusion, assessed as day 0.

Safety will be evaluated by analyzing the type, frequency and severity of adverse events (AE) and by monitoring for systemic reactions (fever, tachycardia, nausea and vomiting, joint pain, skin rash). Overall, 3 study emergent serious adverse events (SAEs) were reported in patients treated with MLM-CAR44.1 T-cells.

GroupValue95% CI
MLM-CAR44.1 T-cells Infusion3
Phase I: Absence of Replication Competent Retrovirus (RCR) in Blood Specimens: 3 Months Post-infusion Primary · 3 months after infusion (assessed as day 0)

The absence of replication competent retrovirus (RCR) in blood specimens: 3 months post-infusion will be monitored by DNA PCR for the Galv gene. RCR search was conducted centrally using a quantitative molecular test, (real time quantitative PCR, q-PCR analysis) determining the absence of RCR by DNA PCR for the Galv and gag-pol genes on genomic DNA from patient's peripheral blood lymphocytes. The objective of this q-PCR analysis is to exclude the presence of RCR originated by recombination with PG13 packaging cell sequences by detecting the Galv and gag-pol transcripts in the transduced cells.

GroupValue95% CI
MLM-CAR44.1 T-cells Infusion2
Phase I: Absence of Replication Competent Retrovirus (RCR) in Blood Specimens: 6 Months Post-infusion Primary · 6 months after infusion (assessed as day 0)

The absence of replication competent retrovirus (RCR) in blood specimens will be monitored by DNA PCR for the Galv gene. RCR search was conducted centrally using a quantitative molecular test, (real time quantitative PCR, q-PCR analysis) determining the absence of RCR by DNA PCR for the Galv and gag-pol genes on genomic DNA from patient's peripheral blood lymphocytes. The objective of this q-PCR analysis is to exclude the presence of RCR originated by recombination with PG13 packaging cell sequences by detecting the Galv and gag-pol transcripts in the transduced cells. The absence of the Galv

GroupValue95% CI
MLM-CAR44.1 T-cells Infusion2
Phase IIa: Hematological Disease Response to MLM-CAR44.1 T-cells in MM Primary · 3 months after T-cell infusion, assessed as day 0

The hematologic disease response will be classified according to IMWG criteria

GroupValue95% CI
MLM-CAR44.1 T-cells Infusion0
Phase I: Hematologic Disease Response to MLM-CAR44.1 T-cells in MM Secondary · 1 and 3 months following T-cell infusion, assessed as day 0

Hematologic disease response evaluated at Day 28 following CART-cell infusion, as overall response rate (ORR), stringent complete response (sCR), CR, very good partial response (VGPR) and partial response (PR).

GroupValue95% CI
MLM-CAR44.1 T-cells Infusion2
MLM-CAR44.1 T-cells Infusion0
Phase I: The Levels of Circulating MLM-CAR44.1 T-cells in Blood Samples Secondary · At day 7, 14, 21, 28, 60, 90, 180 from infusion, assessed as day 0

The levels will be evaluated by flow cytometry and qPCR (in vivo pharmacokinetic profile).

GroupValue95% CI
MLM-CAR44.1 T-cells Infusion1
MLM-CAR44.1 T-cells Infusion1

Adverse events — posted to ClinicalTrials.gov

Time frame: 15 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MLM-CAR44.1 T-cells Infusion
Serious: 2/2 (100%)
Deaths: 1/2

Serious adverse events (2 terms)

ReactionSystemMLM-CAR44.1 T-cells Infusion
PneumoniaInfections and infestations
Disease progressionGeneral disorders
Other adverse events (3 terms — click to expand)

ReactionSystemMLM-CAR44.1 T-cells Infusion
PyrexiaImmune system disorders
NeutropeniaBlood and lymphatic system disorders
AnemiaBlood and lymphatic system disorders

Most-reported serious reactions: Pneumonia, Disease progression.

Data from ClinicalTrials.gov NCT04097301 adverse events section.

Sponsor's own description

The purpose of this first-in-man Phase I-IIa study is to evaluate the safety and antitumor activity of autologous CD44v6 CAR T-cells in patients with acute myeloid leukemia (AML) and multiple myeloma (MM).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies.
    Walcher L, Kistenmacher AK, Suo H, Kitte R, et al · · 2020 · cited 688× · PMID 32849491 · DOI 10.3389/fimmu.2020.01280
  2. Cancer stem cells: advances in knowledge and implications for cancer therapy.
    Chu X, Tian W, Ning J, Xiao G, et al · · 2024 · cited 311× · PMID 38965243 · DOI 10.1038/s41392-024-01851-y
  3. T-cell-based immunotherapy of acute myeloid leukemia: current concepts and future developments.
    Daver N, Alotaibi AS, Bücklein V, Subklewe M. · · 2021 · cited 178× · PMID 33953290 · DOI 10.1038/s41375-021-01253-x
  4. CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions.
    Mardiana S, Gill S. · · 2020 · cited 155× · PMID 32435621 · DOI 10.3389/fonc.2020.00697
  5. CAR T-cell therapy in multiple myeloma: more room for improvement.
    Teoh PJ, Chng WJ. · · 2021 · cited 123× · PMID 33927192 · DOI 10.1038/s41408-021-00469-5
  6. CAR T-Cell Therapy in Hematological Malignancies.
    Haslauer T, Greil R, Zaborsky N, Geisberger R. · · 2021 · cited 115× · PMID 34445701 · DOI 10.3390/ijms22168996
  7. CAR-T cell combination therapy: the next revolution in cancer treatment.
    Al-Haideri M, Tondok SB, Safa SH, Maleki AH, et al · · 2022 · cited 106× · PMID 36419058 · DOI 10.1186/s12935-022-02778-6
  8. Next generations of CAR-T cells - new therapeutic opportunities in hematology?
    Tomasik J, Jasiński M, Basak GW. · · 2022 · cited 98× · PMID 36389658 · DOI 10.3389/fimmu.2022.1034707

Verify or expand the search:

Other recruiting trials for Acute Myeloid Leukemia

Currently open trials in the same condition.

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Trials by the same sponsor.

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