JCAR017 for Chronic Leukemia or Lymphoma

Recruiting at95 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Juno Therapeutics, a Subsidiary of Celgene

Must be taking: Ibrutinib, Venetoclax

Must not be taking: Alemtuzumab, Cladribine

Disqualifiers: Active CNS malignancy, Richter's transformation, others

No Placebo Group

Breakthrough Therapy

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests JCAR017, a therapy using modified immune cells, in adults with hard-to-treat CLL or SLL. It aims to see if these enhanced immune cells can better fight the cancer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications, but certain medications must be stopped before joining. For example, venetoclax must be stopped 4 days before, and some other medications like corticosteroids and anti-CD20 antibodies have specific stop times before starting the trial.

What data supports the effectiveness of the drug JCAR017 for Chronic Leukemia or Lymphoma?

Research indicates that venetoclax, a component of the treatment, is improving outcomes for patients with chronic lymphocytic leukemia, a type of leukemia, when used with other targeted therapies. Additionally, Bruton tyrosine kinase inhibitors, like ibrutinib, are showing potential in making chronic lymphocytic leukemia potentially curable. ^{1 2 3 4 5}

Is lisocabtagene maraleucel (JCAR017) safe for humans?

Lisocabtagene maraleucel (JCAR017) has been shown to have a manageable safety profile in treating large B-cell lymphoma, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues. Patients need to be closely monitored for at least seven days after receiving the treatment. ^{6 7 8 9 10}

How is the drug JCAR017 (lisocabtagene maraleucel) unique for treating chronic leukemia or lymphoma?

JCAR017 (lisocabtagene maraleucel) is a type of CAR T-cell therapy, which is unique because it involves modifying a patient's own immune cells to better recognize and attack cancer cells, offering a personalized approach compared to traditional chemotherapy. ^{11 12 13 14 15}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

Adults with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) who have failed multiple prior therapies can join. Participants must have adequate organ and bone marrow function, not be pregnant, and cannot have active infections like hepatitis B/C or HIV.

Inclusion Criteria

I am eligible for a therapy combining ibrutinib and JCAR017.

My cancer is CD19 positive, even after CD19-targeted treatment.

I have been diagnosed with CLL and need treatment according to my doctor.

Exclusion Criteria

My condition has progressed to Richter's transformation.

I am experiencing severe symptoms from a transplant rejection.

I have a significant brain or nervous system condition.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Phase 1 to determine the recommended dose of JCAR017 monotherapy and assess combinations with ibrutinib and venetoclax

Up to 48 months

Phase 2 Treatment

Phase 2 to further assess the efficacy and safety of JCAR017 monotherapy at the recommended dose

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

Treatment Details

Interventions

• Ibrutinib (Small Molecule)
• JCAR017 (lisocabtagene maraleucel) (CAR T-cell Therapy)
• Venetoclax (Small Molecule)

Trial Overview The trial is testing JCAR017 alone or in combination with either ibrutinib or venetoclax to treat CLL/SLL. It's a multi-phase study starting with finding the right dose of JCAR017 before moving on to test its effectiveness and safety at that dose.

Participant Groups

Group I: Phase 2 JCAR017 monotherapy Experimental Treatment 1 Intervention

Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm

Group II: Phase 2 JCAR017 Double-Exposed Monotherapy Expansion (DEME) Experimental Treatment 1 Intervention

Subjects will receive JCAR017 monotherapy

Group III: Phase 1 JCAR017 monotherapy Experimental Treatment 1 Intervention

Subjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)

Group IV: Phase 1 JCAR017 + venetoclax Experimental Treatment 2 Interventions

Subjects will receive venetoclax as bridging anticancer therapy until lymphodepletion chemotherapy/ JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm. After JCAR017 infusion subjects will receive venetoclax until Day 90.

Group V: Phase 1 JCAR017 + ibrutinib Experimental Treatment 1 Intervention

Subjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm + ibrutinib

Who Is Running the Clinical Trial?

Juno Therapeutics, a Subsidiary of Celgene

Lead Sponsor

Trials

12

Recruited

1,400+

Findings from Research

Recent advancements in leukemia treatments have led to high cure rates, such as over 90% for hairy cell leukemia with cladribine and rituximab, and 80-90% for acute promyelocytic leukemia using all-trans retinoic acid and arsenic trioxide.

Chronic lymphocytic leukemia, once considered incurable, may now be potentially curable with targeted therapies like Bruton tyrosine kinase inhibitors and venetoclax, showcasing the significant progress in leukemia treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cure of leukemia through the optimist's prism. Kantarjian, HM., Jain, N., Garcia-Manero, G., et al.[2023]

Dasatinib has been approved by the FDA as a treatment for pediatric chronic myeloid leukemia, providing a new therapeutic option for young patients.

As the second tyrosine kinase inhibitor approved for this condition, dasatinib can be used in both first- and second-line treatment, expanding the choices available for managing this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib Approved for Pediatric CML. [2019]

Dasatinib is highly effective as an initial treatment for newly diagnosed chronic myeloid leukemia (CML), with 98% of 50 patients achieving a complete cytogenetic response (CCyR) within 3 months and 94% achieving CCyR by 6 months.

The treatment demonstrated a favorable safety profile, with manageable side effects; 21% of patients experienced severe neutropenia, but all patients remained alive after a median follow-up of 24 months, indicating strong long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. Cortes, JE., Jones, D., O'Brien, S., et al.[2023]

Recent advancements in treating lymphoid leukemias have successfully integrated molecular targeted therapies, such as rituximab and BCR-ABL inhibitors, with traditional chemotherapy, enhancing treatment options for conditions like acute lymphoblastic leukemia and chronic lymphocytic leukemia.

The review highlights several investigational agents, including inotuzumab and ibrutinib, which show promise in improving patient outcomes, indicating a shift towards more personalized and effective treatment strategies for lymphoid leukemias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Molecular targeted therapy in lymphoid leukemias]. Kojima, K., Ando, T., Kimura, S.[2014]

Lisocabtagene Maraleucel (Liso-cel) is a promising CAR-T therapy targeting CD19, showing strong antitumor activity in aggressive B-cell lymphomas with manageable toxicity, as confirmed in the TRANSCEND NHL001 trial.

Preclinical studies indicate that a specific ratio of CD4+ and CD8+ T-cells enhances the effectiveness of Liso-cel, suggesting a well-balanced approach to maximizing both efficacy and safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene Maraleucel for the treatment of B-cell lymphoma. Iragavarapu, C., Hildebrandt, G.[2022]

Lisocabtagene maraleucel (Breyanzi) has been approved by the FDA for treating adults with large B-cell lymphoma who have relapsed or are refractory after initial treatment, highlighting its efficacy in a challenging patient population.

Due to the risk of serious side effects like cytokine release syndrome and neurological toxicities, patients must be closely monitored for at least seven days post-infusion, emphasizing the importance of safety in its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approval for Drug Treating Large B-Cell Lymphoma. Aschenbrenner, DS.[2023]

Lisocabtagene maraleucel (liso-cel) is an FDA-approved CAR T-cell therapy specifically for treating relapsed/refractory large B-cell lymphoma, with its approval based on the successful TRANSCEND trial.

The review highlights the unique structure and manufacturing process of liso-cel, as well as its efficacy and safety profile demonstrated in landmark trials, including its evaluation in the second-line treatment setting through the TRANSFORM and PILOT studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel in the treatment of relapsed/refractory large B-cell lymphoma. St-Pierre, F., Gordon, LI.[2023]

In a study involving 344 patients with relapsed or refractory large B-cell lymphomas, lisocabtagene maraleucel (liso-cel) demonstrated a high objective response rate of 73%, with 53% achieving a complete response, indicating its efficacy as a treatment option.

The safety profile of liso-cel was acceptable, with a low incidence of severe cytokine release syndrome (2%) and neurological events (10%), suggesting it can be safely administered to patients with various high-risk features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Abramson, JS., Palomba, ML., Gordon, LI., et al.[2021]

In a study involving 14 Japanese patients with relapsed or refractory aggressive large B-cell lymphoma, the CAR T-cell therapy lisocabtagene maraleucel (liso-cel) showed a 70% objective response rate and a 50% complete response rate, indicating significant efficacy.

The treatment had a manageable safety profile, with common side effects including neutropenia (90%) and cytokine release syndrome (50%), but no severe (grade ≥3) cytokine release syndrome events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Makita, S., Yamamoto, G., Maruyama, D., et al.[2023]

Elacytarabine, a novel ester of ara-C, shows high efficacy against cancer cells that are resistant to standard ara-C treatment, making it a promising option for patients with hematologic malignancies and solid tumors.

Clinical trials indicate that elacytarabine has an acceptable side effect profile while demonstrating encouraging efficacy, suggesting it could become an important treatment for various cancers, with further results from ongoing Phase III trials anticipated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacytarabine--lipid vector technology overcoming drug resistance in acute myeloid leukemia. Burke, AC., Giles, FJ.[2013]

Topotecan shows promise as a treatment for acute myelogenous leukemia (AML) and related conditions, particularly benefiting patients with poor-prognosis chromosome abnormalities (-5,-7), and may be superior to single-agent ara-C in these cases.

Combining topotecan with ara-C is particularly effective in treating refractory anemia with excess blasts (RAEB) and transformation (RAEB-t), and the addition of all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) can improve outcomes for patients with poor cytogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents for the treatment of acute myelogenous leukemia: focus on topotecan and retinoids. Estey, EH.[2013]

In a study of 67 patients with newly diagnosed acute nonlymphocytic leukemia who were poor candidates for standard therapy, 42% achieved complete remission with high-dose ara-C treatment, despite significant risks.

The treatment was associated with high toxicity, leading to a 34% mortality rate during therapy, with factors like poor performance status and low platelet counts linked to higher death rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose cytosine arabinoside as the initial treatment of poor-risk patients with acute nonlymphocytic leukemia: a Leukemia Intergroup Study. Preisler, HD., Raza, A., Barcos, M., et al.[2017]

A second hematopoietic stem cell transplantation (HSCT) using high-dose Ara-C and mitoxantrone was successfully performed in 5 children with refractory or recurrent juvenile myelomonocytic leukemia (JMML), leading to long-term survival without disease recurrence.

All 5 patients remained alive and disease-free for up to 246 months post-transplant, with no significant toxicity reported, indicating that this approach may be a safe and effective option for patients who do not respond to the initial HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytosine arabinoside and mitoxantrone followed by second allogeneic transplant for the treatment of children with refractory juvenile myelomonocytic leukemia. Patel, SA., Coulter, DW., Grovas, AC., et al.[2021]

The study developed seven CEM/ara-C-resistant leukemic clones that showed significant cross-resistance to multiple chemotherapeutic agents and gamma radiation, indicating that resistance to ara-C can lead to reduced effectiveness of other treatments.

The resistance mechanisms identified include overexpression of the anti-apoptotic protein bcl-2 and the presence of P-glycoprotein (P-gp), suggesting that these factors contribute to the survival of resistant cells and may complicate treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytosine arabinoside (ara-C) resistance confers cross-resistance or collateral sensitivity to other classes of anti-leukemic drugs. Martin-Aragon, S., Mukherjee, SK., Taylor, BJ., et al.[2018]

References

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

The cure of leukemia through the optimist's prism. [2023]

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

Targeting BCR-ABL and JAK2 in Ph+ ALL. [2021]

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

Dasatinib Approved for Pediatric CML. [2019]

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

Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

[Molecular targeted therapy in lymphoid leukemias]. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Lisocabtagene Maraleucel for the treatment of B-cell lymphoma. [2022]

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

New Approval for Drug Treating Large B-Cell Lymphoma. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel in the treatment of relapsed/refractory large B-cell lymphoma. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. [2021]

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

Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Elacytarabine--lipid vector technology overcoming drug resistance in acute myeloid leukemia. [2013]

12. England pubmed.ncbi.nlm.nih.gov

New agents for the treatment of acute myelogenous leukemia: focus on topotecan and retinoids. [2013]

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

High-dose cytosine arabinoside as the initial treatment of poor-risk patients with acute nonlymphocytic leukemia: a Leukemia Intergroup Study. [2017]

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

Cytosine arabinoside and mitoxantrone followed by second allogeneic transplant for the treatment of children with refractory juvenile myelomonocytic leukemia. [2021]

15. Greece pubmed.ncbi.nlm.nih.gov

Cytosine arabinoside (ara-C) resistance confers cross-resistance or collateral sensitivity to other classes of anti-leukemic drugs. [2018]