Pediatric-Inspired Chemotherapy for Leukemia

Recruiting at 3 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Ph+ ALL, Burkitt's ALL, 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: Unknown

39 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to find out whether the combination of chemotherapy drugs that are routinely used in children with ALL, will be safe and effective in treating adult patients with ALL. The standard treatment for adults with ALL consists of many chemotherapy drugs that are given in different combinations and in several steps. In adult ALL there is no standard which drugs to give and how to combine them. Some leukemias have a chromosome abnormality called Philadelphia chromosome (also called Ph Positive) and some leukemias do not (called Ph Negative). In this study we want to see whether this combination of chemotherapy drugs will be safe and effective in treating adult patients with Ph Negative ALL.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking medications for conditions like active infections or other serious health issues, you may need to discuss this with the trial team.

What data supports the effectiveness of the drugs used in the Pediatric-Inspired Chemotherapy for Leukemia trial?

Research shows that combinations of drugs like vincristine, dexamethasone, and L-asparaginase are effective in delaying leukemia progression in models, and methotrexate with 6-mercaptopurine has been used successfully in long-term leukemia treatment, achieving high remission rates. ^{1 2 3 4 5}

Is pediatric-inspired chemotherapy for leukemia generally safe in humans?

Pediatric-inspired chemotherapy, including drugs like pegaspargase, methotrexate, and cytarabine, has been studied in both children and adults. While it can be effective, it may cause side effects such as myelosuppression (reduced bone marrow activity), hyperbilirubinemia (high bilirubin levels), and other toxicities. However, these side effects are often manageable, and the treatment has been shown to be safe for many patients. ^{6 7 8 9 10}

How is the Pediatric-Inspired Chemotherapy for Leukemia treatment different from other leukemia treatments?

This treatment is unique because it combines multiple drugs, including 6-Mercaptopurine, Cyclophosphamide, Cytarabine, Daunorubicin, Dexamethasone, PEG-Asparaginase, Prednisone, and Vincristine, to mimic pediatric protocols, which have shown improved outcomes in children. The combination aims to enhance remission rates and survival by using a diverse set of drugs that target leukemia cells in different ways, potentially offering a more comprehensive approach than treatments using fewer drugs. ^{7 11 12 13 14}

Research Team

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults aged 18-60 with newly diagnosed Ph Negative Acute Lymphoblastic Leukemia (ALL) who haven't been treated yet. They must have good kidney, liver, and heart function, an ECOG performance status of 0-2, and be willing to use birth control. People with certain other conditions or previous ALL treatments are excluded.

Inclusion Criteria

My liver is functioning well, with specific blood test levels within normal limits.

I agree to use effective birth control during and for 4 months after treatment.

I have ALL with CNS involvement and can get additional treatments for it.

Exclusion Criteria

I have had treatment for ALL, but only steroids or hydroxyurea.

Pregnant women or women who are breast-feeding

My leukemia is identified as Mature B-cell (Burkitt's).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Phase I

Participants receive the first cycle of chemotherapy drugs

4-6 weeks

Induction Phase II

Participants receive the second cycle of chemotherapy drugs

4-6 weeks

Intensification I

Participants receive the third cycle of chemotherapy drugs

4-6 weeks

Re-induction I

Participants receive the fourth cycle of chemotherapy drugs

4-6 weeks

Intensification II

Participants receive the fifth cycle of chemotherapy drugs

4-6 weeks

Re-induction II

Participants receive the sixth cycle of chemotherapy drugs

4-6 weeks

Maintenance

Participants continue with a long-term treatment part

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• 6-Mercaptopurine
• Cyclophosphamide
• Cytarabine
• Daunorubicin
• Dexamethasone
• Leucovorin
• Methotrexate
• PEG-Asparaginase
• Prednisone
• Vincristine

Trial Overview The trial is testing a 'Pediatric-Inspired' chemotherapy regimen in adults with ALL to see if it's safe and effective. It includes drugs like Daunorubicin and Vincristine among others used in children's treatment protocols for leukemia.

Participant Groups

Group I: Leukemia Patients Experimental Treatment 12 Interventions

The treatment plan has 6 treatment cycles. The cycle names are listed in the following order: Induction Phase I - Induction Phase II - Intensification I - Re-induction I - Intensification II - Re-induction II Each cycle is given over a period of 4-6 weeks and the interval between them can range between 1-3 weeks. Based the patients medical condition, the doctor may decide to change the timing of the drugs, the interval between the drugs in a cycle, or the interval between the cycles. After receiving all cycles you will continue with a 36 months treatment part that is called Maintenance.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lehigh Valley Health Network

Collaborator

Shire

Industry Sponsor

Trials

457

Recruited

96,000+

Pierre S. Sayad

Shire

Chief Medical Officer

MD from Loma Linda University

Flemming Ornskov

Shire

Chief Executive Officer since 2013

PhD in Medicine from Aarhus University

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Lehigh Valley Health Network

Collaborator

Trials

4

Recruited

8,100+

Findings from Research

The combination of vincristine, dexamethasone, and L-asparaginase (VXL) showed synergistic effects in treating pediatric acute lymphoblastic leukemia (ALL) in both laboratory and mouse models, significantly delaying disease progression by up to 146 days.

Pharmacokinetic analysis indicated that the combination therapy increased the systemic exposure of dexamethasone, which may enhance the effectiveness of the treatment, providing a promising platform for testing new drugs in clinical trials for relapsed or refractory ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts. Szymanska, B., Wilczynska-Kalak, U., Kang, MH., 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 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 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 randomized trial involving over 1000 children with standard-risk acute lymphoblastic leukemia (ALL), dexamethasone was found to significantly reduce the risk of central nervous system relapses compared to prednisone, with a 6-year relapse rate of 3.7% versus 7.1%.

The study also showed that dexamethasone improved event-free survival rates at 6 years (85%) compared to prednisone (77%), indicating that dexamethasone may be a more effective treatment option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Bostrom, BC., Sensel, MR., Sather, HN., et al.[2021]

A multicenter phase II clinical trial involving 39 adults aged 20-60 with acute lymphoblastic leukemia (ALL) showed that a pediatric-inspired chemotherapy regimen using pegaspargase resulted in a high complete response rate of 97%.

While the treatment was associated with significant toxicities, such as grade 3-4 hyperbilirubinemia and hypertriglyceridemia, these were manageable, and the overall survival rate at 3 years was 76.4%, indicating that pegaspargase can be safely integrated into intensive chemotherapy for adults with ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia. Geyer, MB., Ritchie, EK., Rao, AV., et al.[2021]

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 pilot study involving 18 children with acute nonlymphoblastic leukemia, 78% achieved complete remission (CR) after treatment, with 50% of those remaining in CR for over 35 months.

The treatment protocol was well tolerated with minimal side effects, suggesting a favorable safety profile, and overall survival rates improved, with 50% of children living for 36 months or longer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a pilot study for the treatment of childhood acute nonlymphoblastic leukemia. Vowels, MR., White, L., Hughes, DO.[2019]

References

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

Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts. [2021]

2. United States 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. [2019]

3. Slovakia pubmed.ncbi.nlm.nih.gov

Treatment of acute lymphoblastic leukemia in children. Long-term results of two trials. [2007]

4. Japan pubmed.ncbi.nlm.nih.gov

Two groups of Philadelphia chromosome-positive childhood acute lymphoblastic leukemia classified by pretreatment multidrug sensitivity or resistance in in vitro testing. [2019]

5. United States 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. [2017]

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

Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group. [2021]

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

Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Treatment of relapsed acute lymphocytic leukemia in adults. [2019]

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

Intensified PEG-L-asparaginase and antimetabolite-based therapy for treatment of higher risk precursor-B acute lymphoblastic leukemia: a report from the Children's Oncology Group. [2018]

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

Results of a pilot study for the treatment of childhood acute nonlymphoblastic leukemia. [2019]

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

Vincristine, prednisone and L-asparaginase in the induction of remission in children with acute lymphoblastic leukemia following relapse. [2019]

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

Treatment intensity and outcome for children with acute lymphocytic leukemia of standard risk. A Pediatric Oncology Group Study. [2019]

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

Long-term results of reinforcement therapy in children with acute leukemia. [2019]