Chemotherapy + Stem Cell Transplant for Acute Lymphoblastic Leukemia

Not currently recruiting at 179 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Tyrosine kinase inhibitors

Disqualifiers: Cardiovascular disease, HIV, 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: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a combination of chemotherapy drugs, with or without a donor stem cell transplant (also known as allogeneic hematopoietic stem cell transplantation), for treating acute lymphoblastic leukemia (ALL). The goal is to determine if this approach can kill more cancer cells and help prevent recurrence. The trial targets patients with ALL who have specific genetic markers and have not yet received certain treatments. Ideal participants are those diagnosed with ALL, showing ALL in their blood or bone marrow, and who have not undergone extensive previous treatment. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients may have received no more than 14 days of tyrosine kinase inhibitor therapy prior to registration, and there are specific time frames for other treatments. 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 shows that the drugs used in this trial for treating acute lymphoblastic leukemia (ALL) have different safety profiles.

Cyclophosphamide requires careful use, especially in patients with active urinary tract infections. The FDA notes that it may cause serious side effects like infertility and birth defects.

Dexamethasone helps reduce the risk of cancer spreading to the brain and spine but may increase the risk of death from treatment compared to prednisone.

Doxorubicin Hydrochloride is approved for some blood cancers, including ALL, but can cause heart problems in about 11% of patients shortly after use.

Methotrexate can cause severe liver damage, including scarring and liver disease, though it is often used with other drugs for ALL.

Methylprednisolone and Prednisone, steroids in the treatment, can change blood cell counts and lead to serious infections.

Vincristine Sulfate is effective against leukemia, but high doses can be deadly, especially in young children.

Finally, donor stem cell transplants are a common approach for some leukemia cases. They can be beneficial but also carry risks like graft-versus-host disease, where donor cells attack the patient's body.

Overall, while these treatments can be effective, they often have significant side effects. The trial aims to better understand these effects when the drugs are used together. Participants should carefully consider these factors and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with stem cell transplants for treating acute lymphoblastic leukemia (ALL) because it offers a potentially more effective approach than current treatments. This combination not only uses powerful chemotherapy agents like Cyclophosphamide and Methotrexate to kill cancer cells but also includes a stem cell transplant to help rebuild the patient’s immune system, which can be severely weakened by the disease and its treatment. This strategy aims to reduce relapse rates and improve long-term survival, making it a promising option compared to standard chemotherapy alone. Additionally, the maintenance phase with drugs like Dexamethasone and Vincristine Sulfate helps in keeping the cancer in remission, offering a comprehensive treatment plan for ALL patients.

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

Research has shown that combining chemotherapy with stem cell transplants can effectively treat acute lymphoblastic leukemia (ALL). In this trial, participants will receive a combination of chemotherapy drugs, including Cyclophosphamide, Dexamethasone, Methotrexate, and Vincristine sulfate, alongside a stem cell transplant. Studies have found that using stem cells from a donor can improve survival rates and lower the chance of cancer returning in adults with ALL. Cyclophosphamide has improved outcomes for ALL patients. Dexamethasone reduces relapses more effectively than prednisone. High doses of Methotrexate have significantly increased the time children with ALL remain free of events like relapses. Vincristine sulfate also helps patients achieve remission. Overall, this combination treatment shows great potential in managing ALL. ^{6 7 8 9 10}

Who Is on the Research Team?

Farhad Ravandi-Kashani

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for patients with acute lymphoblastic leukemia who have not had more than one prior treatment, are not HIV positive, and do not have significant heart disease or other serious health issues. They must be Philadelphia chromosome or BCR/ABL positive and cannot be pregnant. A matched stem cell donor must be available.

Inclusion Criteria

Patients must have immunophenotyping of the blood or marrow lymphoblasts to determine lineage

Patients must meet specific laboratory criteria for bilirubin, liver enzymes, and kidney function

I have been diagnosed with acute lymphoblastic leukemia affecting my bone marrow or blood.

Exclusion Criteria

I have received a stem cell transplant from a donor.

I have been diagnosed with Burkitt's lymphoma.

I have acute myeloid leukemia without spread beyond the bone marrow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction/Consolidation Therapy

Patients receive alternating courses of chemotherapy with hyper-CVAD and dasatinib

16-24 weeks

Multiple visits for each course

Maintenance Therapy

Patients receive vincristine, prednisone, and dasatinib monthly for up to 24 months

24 months

Monthly visits

Allogeneic Stem Cell Transplantation

Patients undergo conditioning regimen followed by stem cell transplantation

1 month

Inpatient stay for transplantation

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Cyclophosphamide
• Dexamethasone
• Doxorubicin Hydrochloride
• Laboratory Biomarker Analysis
• Methotrexate
• Methylprednisolone
• Peripheral Blood Stem Cell Transplantation
• Prednisone
• Total-Body Irradiation
• Vincristine Sulfate

Trial Overview

The study tests if combination chemotherapy with or without a donor stem cell transplant can effectively treat acute lymphoblastic leukemia. It examines how well multiple drugs work together to stop cancer growth and whether a transplant can help the immune system fight cancer cells.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, transplant, maintenance) Experimental Treatment 18 Interventions

See Detailed Description

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 56 untreated childhood acute lymphoblastic leukemia (ALL) patients, the complete remission rates were similar across three treatment regimens, indicating that adding anthracyclines (daunorubicin or adriamycin) did not significantly improve remission outcomes compared to vincristine and prednisone alone.

However, the anthracycline regimens led to increased granulocytopenia and a higher rate of infectious complications, suggesting that while they may offer some theoretical benefits, their use could result in greater morbidity without improving long-term remission or survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): addition of an anthracycline to vincristine and prednisone. Sallan, SE., Camitta, BM., Frei, E., et al.[2019]

In a study involving 408 children with acute lymphoblastic leukemia (ALL), dexamethasone was found to be more effective than prednisone in treatment, but it was associated with poorer performance in fluid reasoning tests among patients.

While most neuropsychological outcomes were similar between the two groups, a higher percentage of patients treated with dexamethasone required special education services (33% vs. 20% for prednisone), suggesting a need for further investigation into the long-term cognitive effects of dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological outcomes of a randomized trial of prednisone versus dexamethasone in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute All Consortium Protocol 00-01. Waber, DP., McCabe, M., Sebree, M., et al.[2021]

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 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]

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]

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