CTX131 for Blood Cancers

Recruiting at 7 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: CRISPR Therapeutics

Must not be taking: Anticancer biologics, Non-biological anticancer

Disqualifiers: CNS pathology, Uncontrolled infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

290 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticancer biologic treatments 30 days before the CTX131 infusion and any non-biological anticancer drugs 14 days before the infusion. Mogamulizumab treatment must be stopped 50 days prior to the infusion.

What data supports the effectiveness of the treatment CTX131 for blood cancers?

The research on CD19 CAR T-cells, which are similar to CTX131, shows they are effective in achieving complete remission and improving overall survival in patients with certain types of blood cancers, like acute lymphoblastic leukemia. ^{1 2 3 4 5}

What makes the treatment CTX131 unique for blood cancers?

CTX131 is a novel treatment that may target specific markers like CD133, which are associated with cancer stem cells in various cancers, potentially offering a new approach to treating blood cancers by focusing on these resistant cell populations. ^{6 7 8 9 10}

What is the purpose of this trial?

This is an open label, multicenter, phase 1/2 dose evaluation and cohort expansion study evaluating the safety and efficacy of CTX131 in subjects with Relapsed/Refractory Hematologic Malignancies

Research Team

Alissa Keegan, MD, PhD

Principal Investigator

CRISPR Therapeutics

Eligibility Criteria

This trial is for adults with certain blood cancers that have come back or didn't respond to treatment. These include various types of lymphoma and acute myeloid leukemia. Participants must meet specific health criteria not detailed here.

Inclusion Criteria

I am mostly active and can care for myself, even if I have AML.

My kidney, liver, heart, and lung functions are all within normal ranges.

I have been diagnosed with a specific type of blood cancer.

Exclusion Criteria

I have a significant brain or nervous system condition.

Positive for HIV, or active hepatitis B virus or hepatitis C virus infection

I haven't had another type of cancer in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CTX131 infusion

1-2 weeks

Treatment

CTX131 is administered by IV infusion following lymphodepleting chemotherapy

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Treatment Details

Interventions

• CTX131

Trial Overview The study is testing CTX131, a new potential treatment for blood cancers. It's an open-label trial, meaning everyone knows they're getting the drug, and it aims to find out how safe it is and how well it works at different doses.

Participant Groups

Group I: CTX131 Experimental Treatment 1 Intervention

Administered by IV infusion following lymphodepleting chemotherapy

Who Is Running the Clinical Trial?

CRISPR Therapeutics

Lead Sponsor

Trials

7

Recruited

630+

Findings from Research

CART19 therapy resulted in a significantly higher complete remission (CR) rate of 90.9% compared to 37.9% in the chemotherapy group, indicating its superior efficacy in treating refractory/relapsed acute lymphoblastic leukemia (R/R ALL).

Patients receiving CART19 therapy also had a higher overall survival rate at 12 months (60.9%) compared to those on chemotherapy (10.1%), demonstrating the potential long-term benefits of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 targeted CAR-T therapy versus chemotherapy in re-induction treatment of refractory/relapsed acute lymphoblastic leukemia: results of a case-controlled study. Wei, G., Hu, Y., Pu, C., et al.[2018]

CD19 CAR T-cells significantly improve complete remission rates compared to blinatumomab and standard chemotherapy, indicating their strong efficacy in treating relapsed/refractory B-cell acute lymphoblastic leukaemia.

Both CD19 CAR T-cells and dual CD19/CD22 CAR T-cells show higher 1-year overall survival rates compared to other treatments like blinatumomab and inotuzumab ozogamicin, suggesting they are effective options for long-term patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the efficacy of salvage regimens for relapsed/refractory B-cell acute lymphoblastic leukaemia: a systematic review and network meta-analysis. Cao, HY., Wan, CL., Xue, SL.[2023]

A 17-year-old girl with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) showed a unique JAK2 mutation, which was identified as a potential therapeutic target, leading to the use of the JAK2 inhibitor ruxolitinib in her treatment.

Incorporating ruxolitinib into a modified chemotherapy regimen allowed her to achieve complete remission with undetectable minimal residual disease (MRD) before undergoing a stem cell transplant, demonstrating the treatment's efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of ruxolitinib into dose-intensified therapy targeted against a novel JAK2 F694L mutation in B-precursor acute lymphoblastic leukemia. Mayfield, JR., Czuchlewski, DR., Gale, JM., et al.[2022]

Cytokine-induced killer (CIK) cells modified to express anti-CD123 CAR are effective in reducing leukemia burden in acute myeloid leukemia (AML) while sparing normal hematopoietic stem/progenitor cells, making them a safer treatment option.

In contrast, anti-CD33 CAR T cells also reduce leukemia but risk damaging normal blood cell production due to CD33 expression on healthy cells, highlighting the potential advantages of targeting CD123 in immunotherapy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Pizzitola, I., Anjos-Afonso, F., Rouault-Pierre, K., et al.[2023]

WHI-P131, a dual-function JAK3 tyrosine kinase inhibitor, was successfully formulated into nanoparticles (WHI-P131-NP) with over 95% encapsulation efficiency, showing strong anti-inflammatory and anti-leukemic effects in preclinical models.

WHI-P131-NP demonstrated superior effectiveness in inducing apoptosis in chemotherapy-resistant leukemia cells and outperformed both WHI-P131 and vincristine in a mouse model, indicating its potential as a promising treatment for resistant leukemias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic nanoparticle constructs of a JAK3 tyrosine kinase inhibitor against human B-lineage ALL cells. Uckun, FM., Dibirdik, I., Qazi, S., et al.[2012]

Acute leukemia (AL) patients show significantly higher expression of CD133 compared to normal controls, with 42.1% of patients testing positive for CD133, indicating its potential role in identifying AL types and predicting treatment outcomes.

The co-expression of CD133 and CD34 in AL patients is associated with a lower complete remission (CR) rate, suggesting that these markers may indicate a poorer prognosis for patients with acute leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The expression of CD133 in acute leukemia and its clinical significance]. Zhou, Y., Meng, HX., Yu, Z., et al.[2016]

In a phase I clinical trial involving 23 patients with advanced CD133-positive tumors, CART-133 cell infusion demonstrated feasibility and manageable toxicities, primarily causing temporary decreases in hemoglobin and platelets.

The treatment resulted in a 65.2% disease control rate over three months, with three patients achieving partial remission and 14 maintaining stable disease, indicating promising efficacy for targeting CD133 in late-stage cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial. Wang, Y., Chen, M., Wu, Z., et al.[2022]

Hepatocellular carcinoma (HCC) is a highly resistant liver cancer, with only 25% of patients suitable for curative treatment, leading to poor survival rates for inoperable cases.

Recent research highlights the role of cancer stem cells (CSCs), particularly CD133(+) liver CSCs, in treatment resistance and tumor recurrence, suggesting that targeting these cells may improve HCC management and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical implications of CD133(+) liver cancer stem cells. Ma, S.[2016]

In a study of 367 pediatric patients with acute myeloid leukemia (AML), high expression of the FLT3 cell-surface receptor (CD135) was found to be associated with specific disease characteristics, such as the FAB M5 subtype and KMT2A rearrangements, but not with FLT3 mutational status.

Despite the variability in CD135 expression, the study concluded that it does not have prognostic significance for clinical outcomes like complete remission rates or overall survival in pediatric AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group. Tarlock, K., Alonzo, TA., Loken, MR., et al.[2022]

In a study of 105 acute myeloid leukaemia (AML) cases, CDw131 expression levels helped identify two subgroups: one with low expression (75 cases) and another with high expression (30 cases), which correlated with distinct biological characteristics.

AMLs with high CDw131 expression were associated with increased cell cycling, specific receptor expressions (like CD11b and CD14), and mutations such as FLT3 internal tandem duplication, suggesting potential targets for new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin (IL)-3/granulocyte macrophage-colony stimulating factor/IL-5 receptor alpha and beta chains are preferentially expressed in acute myeloid leukaemias with mutated FMS-related tyrosine kinase 3 receptor. Riccioni, R., Diverio, D., Riti, V., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

CD19 targeted CAR-T therapy versus chemotherapy in re-induction treatment of refractory/relapsed acute lymphoblastic leukemia: results of a case-controlled study. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Comparing the efficacy of salvage regimens for relapsed/refractory B-cell acute lymphoblastic leukaemia: a systematic review and network meta-analysis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Integration of ruxolitinib into dose-intensified therapy targeted against a novel JAK2 F694L mutation in B-precursor acute lymphoblastic leukemia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic nanoparticle constructs of a JAK3 tyrosine kinase inhibitor against human B-lineage ALL cells. [2012]

6. China pubmed.ncbi.nlm.nih.gov

[The expression of CD133 in acute leukemia and its clinical significance]. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Biology and clinical implications of CD133(+) liver cancer stem cells. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Interleukin (IL)-3/granulocyte macrophage-colony stimulating factor/IL-5 receptor alpha and beta chains are preferentially expressed in acute myeloid leukaemias with mutated FMS-related tyrosine kinase 3 receptor. [2022]