Chemotherapy + Targeted Therapy for Acute Lymphoblastic Leukemia

Overseen By Noah Pinke

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Corticosteroids, Cytarabine

Disqualifiers: Burkitt lymphoma, CNS disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with newly diagnosed acute lymphoblastic leukemia (ALL) who lack the Philadelphia chromosome, a specific genetic marker. The study tests a chemotherapy regimen combined with a targeted therapy called tafasitamab, designed to help the body fight cancer cells more effectively. Researchers aim to determine if adding tafasitamab improves outcomes compared to chemotherapy alone. This trial suits adults with this type of leukemia who cannot follow a pediatric treatment approach due to age or other factors. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in leukemia treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that no prior systemic therapy for ALL is allowed except to control acute symptoms, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the chemotherapy treatment used in this trial, DA-EPOCH, has been tested for safety in earlier studies. These studies found that while the treatment generally works well, patients might experience side effects such as low blood cell counts and infections, which are common with most chemotherapy treatments.

For the targeted therapy component, tafasitamab has been used in other conditions like diffuse large B-cell lymphoma. Common side effects include low blood cell counts and infections. Occasionally, patients needed to pause treatment due to these side effects, a standard approach to managing them.

Overall, both DA-EPOCH and tafasitamab have been studied for safety. However, like any treatment, there can be risks of side effects. Patients should discuss with their healthcare team to understand what to expect and how to manage them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for Acute Lymphoblastic Leukemia because it combines standard chemotherapy drugs with tafasitamab, a targeted therapy that specifically attacks cancer cells expressing the CD19 antigen. This combination aims to enhance the effectiveness of treatment by not only killing cancer cells with chemotherapy but also boosting the immune system's ability to fight the cancer with tafasitamab. Additionally, for CD20 positive patients, the inclusion of rituximab, another targeted therapy, offers a more tailored approach to treating the cancer, potentially improving outcomes beyond what traditional chemotherapy alone can achieve.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that the DA-EPOCH treatment, which participants in this trial may receive, has potential in treating certain types of leukemia. Studies have found it effective in stopping cancer cells from growing and spreading. Evidence from past patients suggests this treatment can lead to significant improvements in people with similar conditions. Tafasitamab, another treatment option in this trial, is a targeted therapy that slows the growth of cancer cells. Early results indicate that adding tafasitamab to DA-EPOCH might enhance its effectiveness in treating Ph- B-ALL. Together, these treatments may offer a stronger approach to fighting this type of leukemia. ^{1 2 3 4 6}

Who Is on the Research Team?

Ryan D. Cassaday

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly-diagnosed Ph- B-ALL who can't use pediatric treatments, often due to age or other concerns. Participants need functioning kidneys and liver (with specific limits on enzyme levels), no severe blood count issues for subsequent treatment cycles, a performance status indicating they're not too sick to participate, and an expected survival beyond 3 months.

Inclusion Criteria

Marrow or blood involvement detectable by MFC

Total bilirubin =< 2.0 x upper limit of normal (ULN) (unless attributed to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point total bilirubin must be =< 4.0 x ULN)

I am an adult with a new diagnosis of a specific type of leukemia.

Exclusion Criteria

May not be pregnant or nursing

I have only received emergency treatment for my acute lymphoblastic leukemia.

I have been diagnosed with Burkitt lymphoma/leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DA-EPOCH+/-R chemotherapy and tafasitamab for up to 8 cycles, with each cycle lasting 21 days

24 weeks

Weekly visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Etoposide
• Prednisone
• Tafasitamab
• Vincristine

Trial Overview The study tests DA-EPOCH+/-R chemotherapy combined with tafasitamab against the same chemo without tafasitamab in treating Ph- B-ALL. The goal is to see if adding the targeted therapy of tafasitamab improves outcomes by slowing cancer cell growth more effectively than chemotherapy alone.

How Is the Trial Designed?

Group I: Treatment (DA-EPOCH+/-R, tafasitamab) Experimental Treatment 12 Interventions

Patients receive etoposide, doxorubicin, and vincristine IV continuously over 96 hours on days 1-4 of each cycle, cyclophosphamide IV over 1 hour on day 5 of each cycle, prednisone PO BID on days 1-5 of each cycle, and tafasitamab IV weekly on days 1, 8, and 15 of each cycle. CD20 positive patients also receive rituximab IV per guidelines on days 1 or 5 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration or biopsy, CT scan, lumbar puncture and undergo blood sample and cerebrospinal fluid collection throughout the trial.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

In a clinical phase II study involving 70 patients with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell non-Hodgkin's lymphoma (NHL), the combination of high-dose idarubicin and high-dose cytosine-arabinoside (ARA-C) resulted in a complete remission rate of 78%.

The treatment was well-tolerated, with limited non-hematologic side effects primarily related to infections, suggesting that this regimen could be a feasible option for patients with difficult-to-treat leukemia without compromising future bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single high dose of idarubicin combined with high-dose ARA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University "La Sapienza" of Rome. Testi, AM., Moleti, ML., Giona, F., et al.[2013]

In a phase II study involving 20 heavily pretreated children with relapsed acute lymphoblastic leukemia (ALL), the combination of ifosfamide and etoposide (VP16) resulted in a 40% complete remission rate, demonstrating significant efficacy in this challenging patient population.

The treatment was generally well tolerated, with myelosuppression being the most common side effect, indicating that while the therapy is effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ifosfamide and etoposide in recurrent childhood acute lymphoblastic leukemia. Crooks, GM., Sato, JK.[2019]

Leukemia cells from children with acute lymphoblast cell leukemia (ALL) showed significantly lower survival rates compared to those from acute myeloblast cell leukemia (AML), indicating that ALL cells may be more sensitive to treatment (p < 0.001).

Interferon-alpha 2b was found to enhance the cytotoxic effects of chemotherapy drugs like cytosar, vepeside, and doxorubicin on leukemia cells, particularly in ALL, suggesting it could be a valuable addition to treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study of tumor cells sensitivity in patients with acute leukemia to cytokines and their combined use with drugs in vitro by MTT analysis]. Litvinova, EA., Mentkevich, GL., Chimishkian, KL.[2016]

In a study of 42 adult patients with poor-risk acute leukemia, the combination of liposomal daunorubicin (DNX) and high-dose arabinosyl cytosine (HDAC) resulted in a high complete remission rate of 51% in acute non-lymphocytic leukemia (ANLL) and 91% in acute lymphocytic leukemia (ALL).

The treatment was associated with low non-hematologic toxicity, making it a safer option for elderly and heavily pretreated patients, with negligible side effects such as no intestinal toxicity and only one case of bacteremia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. Russo, D., Piccaluga, PP., Michieli, M., et al.[2013]

In a study of 31 pediatric patients with relapsed acute lymphoblastic leukemia (ALL), topotecan administered before standard induction therapy resulted in an impressive 89.3% response rate, significantly reducing circulating blast cells.

The combination of topotecan with standard induction therapy led to a 74.2% complete response rate, indicating that this regimen is effective and well-tolerated, despite some hematologic and gastrointestinal toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse. Hijiya, N., Stewart, CF., Zhou, Y., et al.[2015]

In a study of 110 patients with metastatic Ewing sarcoma or primitive neuroectodermal tumor (PNET), the combination of topotecan and cyclophosphamide showed promising activity, with 21 out of 37 patients achieving partial responses.

Amifostine, intended as a cytoprotective agent, did not provide myeloprotection, and overall survival rates remained unchanged compared to previous studies, indicating that while some treatments showed activity, the prognosis for these patients remains poor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. Bernstein, ML., Devidas, M., Lafreniere, D., et al.[2013]

In a study of 365 adults with acute lymphoblastic leukemia (ALL), those treated with the HCVAD chemotherapy regimen had a higher complete remission rate (91%) and better three-year event-free survival (40%) compared to those treated with the VAD regimen (73% and 23%, respectively).

The persistence of peripheral blood blasts on day 7 (D7PBb) and bone marrow blasts on day 14 (D14BMb) after starting chemotherapy had different prognostic implications depending on the treatment regimen, highlighting the importance of early clearance of leukemia cells for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence of peripheral blood and bone marrow blasts during remission induction in adult acute lymphoblastic leukemia confers a poor prognosis depending on treatment intensity. Cortes, J., Fayad, L., O'Brien, S., et al.[2015]

In a study involving 105 children with late bone marrow relapses of acute lymphoblastic leukemia (ALL), 97% achieved a second complete remission, indicating that retreatment can be effective.

The trial did not conclusively determine a superior treatment regimen between doxorubicin/prednisone and cytarabine/teniposide, but identified key prognostic factors such as age under 10, lower white blood cell count at relapse, and longer initial remission duration that are associated with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. Sadowitz, PD., Smith, SD., Shuster, J., et al.[2021]

In a study of 88 children with acute lymphoblastic leukemia, two treatment protocols showed high complete remission rates of 92-96%, with protocol 0276/A demonstrating a significantly lower relapse rate of 4% compared to 28% in protocol 0171.

The long-term outcomes were promising, with 60% of children from protocol 0171 remaining alive in complete remission for over 10 years, while protocol 0276/A showed even better results with over 70% of complete responders in continuous remission for up to 57 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute lymphoblastic leukemia in children. Long-term results of two trials. Cáp, J., Koza, I., Misíková, Z., et al.[2007]

In a clinical phase II study involving 70 patients with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL), 78% achieved complete remission with the combination of high-dose idarubicin and high-dose cytosine-arabinoside, indicating strong antileukemic activity.

The treatment was well-tolerated, with limited non-hematologic side effects primarily related to infections, suggesting that this regimen could be a feasible option for patients while still allowing for potential bone marrow transplantation afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single high dose of idarubicin combined with high-dose ABA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University La Sapienza of Rome. Testi, AM., Moleti, ML., Giona, F., et al.[2013]

In a study testing 11 anti-cancer agents on 4 pediatric ALCL cell lines, vinblastine was found to be the most effective, significantly inhibiting cell growth in a time- and dose-dependent manner, with effective doses as low as 0.0002 microM/L after 24 hours.

Vinblastine treatment not only inhibited cell growth but also induced apoptosis and disrupted mitotic spindle formation, supporting its use as a first-line treatment in high-risk pediatric ALCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antineoplastic agents for pediatric anaplastic large cell lymphoma: Vinblastine is the most effective in vitro. Muto, A., Nakagawa, A., Shimomura, Y., et al.[2019]

In a study of 50 children with acute lymphoblastic leukemia (ALL) who were in their first to fifth relapse, a three-drug reinduction regimen including etoposide (VP-16) led to a complete remission in 34% of patients who received at least two courses of treatment.

The results suggest that prior resistance to teniposide (VM-26) does not prevent patients from responding to VP-16, indicating that higher doses and more frequent administration of VP-16 may effectively overcome resistance, although further research is needed for long-term treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia. Abromowitch, M., Bowman, WP., Ochs, J., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10357946/

Phase II Study of Dose-Adjusted EPOCH as Initial Therapy for ... Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03023046

NCT03023046 | Etoposide, Prednisone, Vincristine Sulfate ... This phase II trial studies how well etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin (DA-EPOCH) works in treating patients ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6540

Initial results from a phase II study of dose-adjusted ... We hypothesized that adding tafa to DA-EPOCH ± R in adults with ND Ph- B-ALL would improve rates of early MRD- without an increase in toxicity.

4. eviq.org.au eviq.org.au/haematology-and-bmt/lymphoma/other-b-cell-lymphoma/783-da-r-epoch-dose-adjusted-rituximab-etoposide

783-DA-R-EPOCH (dose adjusted rituximab etoposide ... This study was designed to assess the efficacy and safety of an infusional DA-EPOCH (dose-adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/ ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02538926

NCT02538926 | Etoposide, Prednisone, Vincristine Sulfate ... This phase II trial studies how well etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride with asparaginase work in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4731284/

Infusional etoposide, cyclophosphamide, vincristine ... The goal of this study was to examine risk factors and outcomes in patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH.