Chemotherapy for Leukemia and Lymphoma

Not currently recruiting at 265 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: CNS3 leukemia, Testicular leukemia, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 14

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of different chemotherapy drug combinations for children and young people with certain blood cancers, specifically acute lymphoblastic leukemia (ALL) and B-lineage lymphoblastic lymphoma that has not spread. The study examines how varying doses and combinations of chemotherapy drugs can more effectively kill cancer cells. Those with newly diagnosed, standard-risk acute lymphoblastic leukemia or localized B-lineage lymphoblastic lymphoma may be suitable for this trial, particularly if their initial white blood cell count was less than 50,000/uL. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should not have received any prior cytotoxic chemotherapy for their current diagnosis, except for certain steroid 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 vincristine sulfate, a drug used in these chemotherapy treatments, has FDA approval for treating acute leukemia. However, it can cause nerve problems and may damage tissue if it leaks from the vein during injection.

Studies have found that dexamethasone usually causes mild to moderate side effects, which often resolve on their own. This drug should not be used during pregnancy, as it can harm the unborn baby.

Research on methotrexate indicates serious risks, such as liver and lung problems, and it may increase the risk of other cancers. However, it has been proven safe for treating cancer in children.

Mercaptopurine, another drug used, also has FDA approval for treating leukemia in both children and adults. However, it can increase the risk of other cancers and cause stomach issues like nausea and vomiting.

In summary, while these drugs have known side effects, they are well-researched and approved for leukemia treatment, providing a level of safety assurance. Participants should discuss potential risks and benefits with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a risk-adapted approach to chemotherapy for leukemia and lymphoma. Unlike standard treatments that might apply a one-size-fits-all regimen, these treatments adjust doses and schedules based on the patient's specific risk factors. This personalization could potentially improve effectiveness and reduce unnecessary side effects. Additionally, the use of medications like higher-dose methotrexate and a combination of both oral and intravenous drugs aims to target cancer cells more aggressively while maintaining patient safety. This tailored approach could represent a significant advancement over current standard treatments.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

Research shows that the chemotherapy treatments in this trial include drugs such as vincristine sulfate, dexamethasone, methotrexate, and mercaptopurine. Participants in the different treatment arms will receive various combinations and dosages of these drugs. Vincristine sulfate has proven effective over the long term for certain types of lymphoma, with 64% of patients not experiencing disease progression and 87% surviving for 10 years. Dexamethasone is stronger than similar drugs and has helped many patients achieve complete remission. Methotrexate has shown a 29.9% complete response rate in some cancers, and mercaptopurine helps maintain longer remissions in acute leukemia. These drugs work together by killing cancer cells, stopping them from dividing, or preventing them from spreading, aiming to effectively treat leukemia and lymphoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Anne L Angiolillo

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with newly diagnosed standard-risk acute lymphoblastic leukemia or localized B-lineage lymphoblastic lymphoma. They must not have had previous cancer treatments, except certain steroids or intrathecal cytarabine. Patients need to agree to use effective contraception if applicable and meet all study requirements.

Inclusion Criteria

Your white blood cell count at the start of the study should be less than 50,000 cells per microliter.

All patients and/or their parents or legal guardians must sign a written informed consent

B-ALL patients must be enrolled on AALL08B1 or APEC14B1 (if open for the classification of newly diagnosed ALL patients) prior to treatment and enrollment on AALL0932

Exclusion Criteria

I haven't had chemotherapy for my current B-ALL/B-LLy or any cancer before starting the AALL0932 protocol, except for steroids or intrathecal cytarabine.

Lactating females unless they have agreed not to breastfeed their infants

I am not pregnant or have a negative pregnancy test if of childbearing age.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive a combination of intrathecal cytarabine, vincristine sulfate, dexamethasone, pegaspargase, and methotrexate to induce remission

4 weeks

Weekly visits for drug administration

Consolidation Therapy

Patients receive vincristine sulfate, mercaptopurine, and methotrexate to consolidate remission

4 weeks

Weekly visits for drug administration

Interim Maintenance I

Patients receive vincristine sulfate and methotrexate to maintain remission

8 weeks

Visits on days 1, 11, 21, 31, and 41

Delayed Intensification

Patients receive a combination of dexamethasone, vincristine sulfate, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, thioguanine, and cytarabine to intensify treatment

8 weeks

Frequent visits for drug administration

Interim Maintenance II

Patients receive vincristine sulfate and methotrexate to maintain remission

8 weeks

Visits on days 1, 11, 21, 31, and 41

Maintenance Therapy

Patients receive vincristine sulfate, dexamethasone, methotrexate, and mercaptopurine to maintain remission over a long-term period

2-3 years

Courses repeat every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Cytarabine
• Dexamethasone
• Doxorubicin Hydrochloride
• Leucovorin Calcium
• Mercaptopurine
• Methotrexate
• Pegaspargase
• Thioguanine
• Vincristine Sulfate

Trial Overview

The trial tests different combinations of chemotherapy drugs on younger patients with specific types of leukemia or lymphoma. It aims to find the best mix and dosage that kills the most cancer cells while monitoring side effects through various stages of treatment.

How Is the Trial Designed?

Group I: Arm SR DS (12-week cycle maintenance) Experimental Treatment 13 Interventions

See Detailed Description

Group II: Arm LR-M (risk-adapted chemotherapy) Experimental Treatment 8 Interventions

Patients receive consolidation and maintenance therapy. See detailed description.

Group III: Arm LR-C (risk-adapted chemotherapy) Experimental Treatment 12 Interventions

Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.

Group IV: Arm D (risk-adapted chemotherapy) Experimental Treatment 7 Interventions

Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

Group V: Arm C (risk-adapted chemotherapy) Experimental Treatment 7 Interventions

Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

Group VI: Arm B-LLy (4-week cycle maintenance) Experimental Treatment 13 Interventions

See Detailed Description.

Group VII: Arm B (risk-adapted chemotherapy) Experimental Treatment 7 Interventions

Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

Group VIII: Arm A (risk-adapted chemotherapy) Experimental Treatment 7 Interventions

Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

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?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 46 elderly patients (aged 69 and older) with aggressive non-Hodgkin's lymphoma, the chemotherapy regimen (CTVP) combined with granulocyte colony-stimulating factor (G-CSF) resulted in a 74% objective response rate and a 46% complete response rate, demonstrating its efficacy.

The use of G-CSF helped reduce severe neutropenia complications, with only 22% experiencing grade 3 or 4 neutropenia, allowing for outpatient treatment without negatively impacting overall survival (47%) or event-free survival (28%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte. Guerci, A., Lederlin, P., Reyes, F., et al.[2020]

In a study of 389 young patients with good-prognosis aggressive lymphoma, the high dose of CHOEP-21 did not improve event-free or overall survival compared to the standard CHOEP-21 regimen, indicating no clinical benefit from the increased dosage.

The high CHOEP regimen was associated with significantly higher toxicity, including increased rates of severe leukocytopenia, thrombocytopenia, infections, and therapy-related deaths, suggesting that the risks may outweigh any potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Pfreundschuh, M., Zwick, C., Zeynalova, S., et al.[2020]

Pegfilgrastim significantly reduces the incidence of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) compared to no prophylaxis, with evidence from 41 studies including randomized controlled trials and observational studies.

The efficacy and safety profiles of other long-acting G-CSFs, such as lipegfilgrastim and balugrastim, are comparable to pegfilgrastim, although results for other long-acting G-CSFs were mixed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review. Pfeil, AM., Allcott, K., Pettengell, R., et al.[2021]

In a phase I pilot study involving 18 patients with refractory lymphoid malignancies, the MILD chemotherapy regimen (methotrexate, ifosfamide, l-asparaginase, and dexamethasone) demonstrated a 57% overall response rate, with complete responses in 3 patients and partial responses in 4 patients.

The treatment was generally feasible with acceptable toxicity, although one patient experienced treatment-related death from systemic mucormycosis, and significant hematologic toxicities were observed, particularly in patients with T/NK-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of combination chemotherapy with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD) for refractory lymphoid malignancies: a pilot study. Tsukune, Y., Isobe, Y., Yasuda, H., et al.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2930949/

Dexamethasone compared to prednisolone for adults with ...

Overall, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) patients in the prednisolone group achieved a complete remission after induction ...

2.

ashpublications.org

ashpublications.org/blood/article/137/23/3272/475147/Prognostic-impact-of-corticosteroids-on-efficacy

Prognostic impact of corticosteroids on efficacy of chimeric ...

Higher cumulative dose of corticosteroids is associated with early progression after CAR-T therapy in large B-cell lymphoma.

3.

clinical-lymphoma-myeloma-leukemia.com

clinical-lymphoma-myeloma-leukemia.com/article/S1557-9190(11)70190-1/fulltext

Successful Use of Full-Dose Dexamethasone, High ...

The patients had a partial remission and complete remission, respectively. These data suggest that DHAP is a safe and effective regimen that can be used without ...

4.

haematologica.org

haematologica.org/article/view/11850

Dexamethasone is associated with reduced frequency and ...

Dexamethasone is associated with reduced frequency and intensity of cytokine release syndrome compared with alternative corticosteroid regimens ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497124069350

Dexamethasone Is More Potent Than Prednisone in B- ...

These data indicate that dex is, on average, 9-10 times more potent than pred, but that the optimal dose ratio is variable between specimens.

6.

merck.com

merck.com/docs/product/safety-data-sheets/ah-sds/Dexamethasone%20Solid%20Formulation_AH_CA_EN.pdf

Dexamethasone Solid Formulation | Safety Data Sheet

Precautionary Statements. : Prevention: P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read.

7.

merck.com

merck.com/docs/product/safety-data-sheets/ah-sds/Dexamethasone%20Formulation_AH_MX_EN.pdf

SAFETY DATA SHEET Dexamethasone Formulation

P202 Do not handle until all safety precautions have been read and understood. P261 Avoid breathing mist or vapors. P272 Contaminated work ...

8.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK482130/

Dexamethasone - StatPearls - NCBI Bookshelf - NIH

Dexamethasone is administered with anti-myeloma products that can cause embryo-fetal harm and are contraindicated for use in pregnancy. Human Data suggests that ...

9.

webmd.com

webmd.com/drugs/2/drug-6751/dexamethasone-sodium-phosphate-injection/details

Dexamethasone (Decadron) - Uses, Side Effects, and More

Find patient medical information for Dexamethasone (Decadron) on WebMD including its uses, side effects and safety, interactions, pictures,

10.

ashpublications.org

ashpublications.org/blood/article/138/Supplement%201/4557/478021/Very-High-Dose-Dexamethasone-Mobilizes-Endogenous

Very-High Dose Dexamethasone Mobilizes Endogenous Bi ...

The murine model safety findings correlate to the human experience. Adverse events reported to date have been self-limiting and mild to moderate ...