Combination Therapy for Acute Lymphoblastic Leukemia

Recruiting at 3 trial locations

Overseen By Seth E. Karol, MD

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Pregnant, Breastfeeding, Prior cancer therapy, 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: 1

Duration: 1 week

850 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the best initial treatment for children and teens newly diagnosed with certain types of leukemia (a blood cancer) or lymphoma (cancer in the lymph nodes). It combines several medicines, including Cytarabine, Daunorubicin, Dexamethasone, Methotrexate, and Vincristine, to evaluate their effectiveness together while gathering more information about each patient's cancer. Researchers also seek to collect data to better understand these cancers and enhance future treatments. Eligible participants include those diagnosed with acute lymphoblastic leukemia, lymphoblastic lymphoma, or mixed phenotype acute leukemia who have received minimal prior treatment. As a Phase 4 trial, this research focuses on understanding how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow for some prior treatments like one dose of certain chemotherapy drugs or steroids. It's best to discuss your specific medications with the trial team.

What is the safety track record for these treatments?

Previous studies have shown varying levels of safety for the combination of treatments used in this trial, which includes dexamethasone, vincristine, daunorubicin, methotrexate, and cytarabine.

Research indicates that dexamethasone is effective but may cause side effects such as increased infection risk, bone issues, and mood changes. Vincristine, approved by the FDA for treating leukemia, can lead to nerve damage and other serious side effects if not used correctly.

Daunorubicin effectively treats leukemia but may cause heart problems and lower blood cell counts. Methotrexate requires careful monitoring due to potential serious side effects, such as liver and kidney damage. Cytarabine, often used with other drugs, can affect blood and bone marrow.

Each of these treatments has been used in leukemia, with safety records showing both benefits and risks. This trial is in a later stage (Phase 4), indicating that the treatments have undergone some safety testing. However, participants should be aware of these potential risks and discuss them with the study team. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this combination therapy for acute lymphoblastic leukemia (ALL) because it integrates multiple drugs that target cancer cells in different ways, potentially improving treatment effectiveness. Unlike traditional treatment regimens, this approach includes an intrathecal triple therapy, which delivers methotrexate, hydrocortisone, and cytarabine directly to the central nervous system, potentially reducing the risk of cancer spreading to the brain. Additionally, combining dexamethasone, vincristine, and daunorubicin may offer a more comprehensive attack on leukemia cells, targeting different stages of cell growth and division, which could lead to better outcomes for patients.

What is the effectiveness track record for this combination therapy in treating acute lymphoblastic leukemia?

This trial will evaluate a combination of specific drugs—dexamethasone, vincristine, daunorubicin, intrathecal methotrexate, and cytarabine—for treating acute lymphoblastic leukemia (ALL). Studies have shown that this drug mix reduces the chance of leukemia returning by attacking cancer cells in multiple ways. Patients treated with this combination have demonstrated better survival rates because it targets cancer cells at different growth stages. This treatment uses a mix of drugs to kill cancer cells and prevent their spread. Overall, this combination has proven effective in providing strong initial treatment for newly diagnosed ALL and related conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Seth E. Karol, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children and teens aged 1 to nearly 19 with newly diagnosed acute leukemia or lymphoma, including ALL with significant bone marrow involvement, LLy with less than 25% bone marrow blasts, or MPAL. It's not for those who are pregnant/breastfeeding, have had certain cancer treatments already (except limited cases), are ineligible for related studies, can't consent, or have specific pre-existing conditions.

Inclusion Criteria

I have been diagnosed with acute leukemia or lymphoma.

My leukemia involves over 25% of my bone marrow or is present in my blood.

I have a type of leukemia that may or may not affect my bone marrow.

Exclusion Criteria

Pregnant or breastfeeding

Known to be currently ineligible for available SJALL therapeutic studies (e.g. receipt of prohibited therapy, no appropriate SJALL therapeutic study available, enrolled on competing trial, etc.)

I've had limited cancer treatment, excluding steroids, which I may have received.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive 7 days of chemotherapy including dexamethasone, vincristine, daunorubicin, and intrathecal triple therapy

1 week

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Regular visits (in-person)

Long-term follow-up

Participants are monitored for overall survival and event-free survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin
• Dexamethasone
• Methotrexate
• Vincristine

Trial Overview The study tests initial therapy while determining the risk category of B-cell Acute Lymphoblastic Leukemia/Lymphoblastic Leukemia. It involves drugs like Dexamethasone and Vincristine among others. The aim is to gather data on the disease and survival rates while creating a database of genomic/clinical information.

How Is the Trial Designed?

Group I: Newly diagnosed ALL, LLy, and MPAL patients Experimental Treatment 6 Interventions

All eligible patients receive the following intervention: Dexamethasone, Vincristine, Daunorubicin, Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)

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

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

In a study involving 490 children with high-risk B-precursor acute lymphoblastic leukemia (ALL), two treatment regimens were compared, showing that both regimens achieved a high remission rate of 97%.

While regimen B, which involved more intensive myelosuppressive combinations, showed a higher estimated 4-year event-free survival (EFS) of 69.4% compared to 61.6% for regimen A, the difference was not statistically significant, and regimen B was associated with more frequent toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial. Lauer, SJ., Shuster, JJ., Mahoney, DH., et al.[2019]

The study found that sequential treatment with methotrexate (MTX) followed by 6-mercaptopurine (6MP) significantly increased apoptosis in a human T-cell leukemia line compared to using each drug alone, suggesting a more effective treatment strategy for childhood acute lymphoblastic leukemia.

Similarly, sequential exposure to tiazofurin (TF) followed by 6-thioguanine (TG) also resulted in a greater induction of apoptosis, indicating that the order of drug administration is crucial for maximizing therapeutic efficacy in leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy in childhood leukaemia: in vitro studies of thiopurines and inhibitors of purine metabolism on apoptosis. De Abreu, RA., Trueworthy, RC., van Kuilenburg, AB., et al.[2017]

A new treatment protocol using teniposide (VM-26) and cytarabine (ara-C) significantly improved event-free survival (EFS) rates in children with acute lymphoblastic leukemia and high initial leukocyte counts, achieving a 44% EFS rate compared to just 10% in matched controls after 4 years.

The combination therapy was well tolerated, with most complications being manageable, and 25 patients from the treatment group survived without adverse events for up to 6.8 years, indicating a promising long-term outcome for this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count greater than or equal to 100 x 10(9)/L. Dahl, GV., Rivera, GK., Look, AT., et al.[2017]

A study involving 428 children with acute lymphoblastic leukemia (ALL) compared two chemotherapy schedules using intermediate-dose methotrexate and cytarabine, finding that both regimens had similar efficacy in maintaining remission but differed in toxicity profiles.

The front-loading regimen resulted in a significantly higher incidence of central nervous system (CNS) toxicity, including permanent leukoencephalopathy in one patient, highlighting the need to balance efficacy with safety in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two schedules of intermediate-dose methotrexate and cytarabine consolidation therapy for childhood B-precursor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Land, VJ., Shuster, JJ., Crist, WM., et al.[2017]

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 83 children with higher-risk B-lineage acute lymphoblastic leukemia (ALL), 98% achieved remission after receiving intensive intravenous methotrexate (MTX) and mercaptopurine (MP) treatment, indicating high efficacy of this regimen.

The 4-year event-free survival rate was 57.4%, and the treatment was associated with generally mild toxicities, suggesting that intensive MTX/MP is an effective and relatively safe option for postremission therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk non-T, non-B acute lymphocytic leukemia: A Pediatric Oncology Group study. Camitta, B., Mahoney, D., Leventhal, B., et al.[2017]

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 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 pilot study involving 106 children with newly diagnosed non-T-, non-B-cell acute lymphoblastic leukemia, the addition of intermediate-dose methotrexate and cytosine arabinoside to standard therapy showed manageable toxicity, primarily neutropenia and fever.

The study found that event-free survival rates at 4 years were 71% for standard-risk patients and 53% for poor-risk patients, suggesting that this treatment approach may be beneficial and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of intermediate-dose methotrexate and cytosine arabinoside, "spread-out" or "up-front," in continuation therapy for childhood non-T, non-B acute lymphoblastic leukemia. A Pediatric Oncology Group study. Krance, RA., Newman, EM., Ravindranath, Y., et al.[2019]

In a study of 33 patients with relapsed acute lymphoblastic leukemia (ALL), 64% achieved complete remission after a combination treatment involving multiple chemotherapy agents, indicating the treatment's efficacy.

While the treatment was effective in inducing remissions, it was associated with significant side effects, particularly hematological issues and infections, suggesting that while the therapy is tolerable, improvements in disease-free survival are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of relapsed acute lymphocytic leukemia in adults. Freund, M., De Boben, M., Diedrich, H., et al.[2019]

In a study of 36 patients with relapsed or refractory acute lymphoblastic leukemia (ALL) treated with an idarubicin-based regimen, the 'ABC' phase II trial achieved a complete remission (CR) rate of 61%, indicating that this treatment approach can be effective for some patients.

Despite the treatment's feasibility and a median overall survival of 7.6 months, there were no long-term survivors, highlighting the ongoing challenge of curing refractory or relapsing ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients. Di Bona, E., Pogliani, E., Rossi, G., et al.[2019]

Citations

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NCT01190930 | Risk-Adapted Chemotherapy in Treating ... All patients receive induction therapy comprising intrathecal (IT) cytarabine on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone orally ( ...

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Cytarabine Injection Cytarabine Injection in combination with other approved anti-cancer drugs is indicated for remission induction in acute non-lymphocytic leukemia of adults and ...

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Cytarabine - StatPearls - NCBI Bookshelf Cytarabine is a medication used in the management and treatment of leukemias and lymphomas. It belongs to the antimetabolic group of medications.

8. go.drugbank.com go.drugbank.com/drugs/DB00987

Cytarabine: Uses, Interactions, Mechanism of Action Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal leukemia.

9. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=15023

Cytarabine Injection BP Cytarabine is indicated primarily for induction and maintenance of remission in acute myelocytic leukaemia of both adults and children.

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The Clinical Safety and Efficacy of Cytarabine ... Grade 3–5 adverse events were reported across nine systems, with the most severe affecting hematology/oncology (282 events, 40%), followed by ...