Chemotherapy + Stem Cell Transplant for Acute Lymphoblastic Leukemia

Recruiting at 173 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

97 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial is studying the side effects of giving combination chemotherapy together with or without donor stem cell transplant and to see how well it works in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

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.

What data supports the effectiveness of the treatment for acute lymphoblastic leukemia?

Research shows that intensive combination chemotherapy, including drugs like prednisone, vincristine, and doxorubicin, can induce remission in children with acute lymphoblastic leukemia, with some achieving long-term survival. Additionally, dexamethasone has been found to be more effective than prednisone, although it may have more side effects. ^{1 2 3 4 5}

Is the chemotherapy and stem cell transplant treatment for acute lymphoblastic leukemia generally safe?

The treatment involves drugs like dexamethasone and prednisone, which have been associated with increased risk of infections and other toxicities. Adding anthracyclines like daunorubicin can increase the risk of infections and other side effects, although they may help reduce leukemia cells more quickly. ^{2 4 6 7 8}

What makes the chemotherapy and stem cell transplant treatment for acute lymphoblastic leukemia unique?

This treatment combines chemotherapy drugs with a stem cell transplant, which is not a standard approach for acute lymphoblastic leukemia. The combination of multiple chemotherapy drugs, such as Cyclophosphamide and Doxorubicin, with a stem cell transplant aims to improve outcomes by using high-dose chemotherapy to kill cancer cells and then replenishing the body's blood-forming cells with healthy stem cells. ^{1 9 10 11 12}

Research Team

Farhad Ravandi-Kashani

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

References

1. England 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. [2019]

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

Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia. [2017]

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

Cyclic combination chemotherapy for acute lymphoblastic leukemia recurring after elective cessation of therapy. [2019]

4. United States 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. [2021]

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

Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. [2021]

6. United States 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. [2019]

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

Dexamethasone-associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin. [2015]

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

Infectious toxicity of dexamethasone during all remission-induction chemotherapy: report of two cases and literature review. [2013]

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

Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. [2021]

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

Treatment of adults with acute lymphoblastic leukemia: do the specifics of the regimen matter?: Results from a prospective randomized trial. [2013]

11. Germany pubmed.ncbi.nlm.nih.gov

Treatment of adult acute lymphoblastic leukemia. Preliminary results of a trial from the French Group. [2019]

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

Adriamycin in combination chemotherapy of adult acute lymphoblastic leukemia: a Southwest Oncology Group study. [2019]