Vinblastine/Prednisone vs. Cytarabine for Histiocytosis

Recruiting at 9 trial locations

Overseen By Carl E. Allen, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Baylor College of Medicine

Must not be taking: Chemotherapies

Disqualifiers: Severe renal, hepatic disease, HIV, 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: 2

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare two treatments for Langerhans Cell Histiocytosis (LCH), a type of cancer where abnormal immune cells can cause damage in the body. The study will evaluate the effectiveness of a single drug, cytarabine (a chemotherapy medication), against the standard treatment of vinblastine and prednisone. Researchers will use PET scans to better identify cancer-affected areas and assess treatment effectiveness. Individuals with a confirmed diagnosis of LCH who haven't received certain previous treatments might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had prior systemic chemotherapy for LCH or other cancers. If you have been on steroids, there are specific limits on how long you can have taken them before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cytarabine is generally safe for individuals with certain types of cancer, including some forms of histiocytosis. Studies indicate that in moderate amounts, cytarabine is effective, and most individuals do not experience severe side effects. One study found that all patients survived, which is very encouraging.

Vinblastine and prednisone are often used as standard treatments for Langerhans Cell Histiocytosis (LCH), having been tested extensively and considered safe for many individuals.

Overall, both treatments in this study are generally safe, but like any treatment, some side effects may occur. It is always advisable to discuss potential risks and benefits with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of cytarabine for histiocytosis because it offers a different approach compared to the standard treatment with vinblastine and prednisone. Unlike the standard of care, which combines chemotherapy and a corticosteroid, cytarabine is a single-agent chemotherapy that specifically targets rapidly dividing cells. This targeted action may lead to effective treatment outcomes with potentially fewer side effects due to the absence of a corticosteroid. Additionally, cytarabine's unique mechanism could provide an alternative for patients who do not respond well to the current standard treatments.

What evidence suggests that this trial's treatments could be effective for LCH?

Research has shown that cytarabine, which participants may receive in the cytarabine arm of this trial, works well for treating Langerhans Cell Histiocytosis (LCH), especially in adults. Studies have found that using cytarabine alone is both safe and effective for people with this condition. Specifically, patients taking cytarabine have experienced positive results, with a decrease in disease activity. Meanwhile, vinblastine and prednisone, part of the standard treatment arm in this trial, are the usual treatments for LCH. These drugs help manage the disease by slowing the growth of LCH cells. Both treatments in this trial aim to control the spread of LCH and ease symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Olive Eckstein, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals aged 0-21 with a confirmed diagnosis of Langerhans cell histiocytosis (LCH), who have not had previous chemotherapy, except steroids. They must be able to perform daily activities at least half the time and cannot have disease limited to just one skin or bone site. Those with severe kidney or liver disease unrelated to LCH, pregnant or breastfeeding females, and patients not using birth control are excluded.

Inclusion Criteria

I am able to perform most of my daily activities without assistance.

My diagnosis of Langerhans cell histiocytosis is confirmed by a biopsy.

I am 21 years old or younger.

Exclusion Criteria

My cancer is not limited to just my skin or bones, with certain exceptions.

My kidney function is not severely impaired.

Patients who are HIV positive may not be enrolled

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Therapy I

Participants receive either cytarabine or vinblastine/prednisone treatment for 6 weeks

6 weeks

Weekly visits for treatment and assessment

Initial Therapy II

Continuation of initial therapy for participants with partial response or stable disease

6 weeks

Weekly visits for treatment and assessment

Continuation Therapy

Long-term continuation of treatment based on response, up to one year

40 weeks

Monthly visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits at 1, 3, 6, 9, 12, 18, 24 months, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Prednisone
• Vinblastine

Trial Overview The study compares two treatments for LCH: vinblastine/prednisone versus cytarabine alone. It aims to determine which therapy is more effective as a first-line treatment and will use PET scans to better identify affected areas and monitor response. The study also seeks correlations between genetic markers in blood/cancer cells and treatment outcomes.

How Is the Trial Designed?

Group I: Cytarabine ("experimental") arm Experimental Treatment 1 Intervention

On this arm, patients will receive single therapy with cytarabine.

Group II: Vinblastine/prednisone ("standard") arm Active Control 1 Intervention

On this arm, patients will receive standard-of-care therapy with vinblastine and prednisone.

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?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

In a study of 143 untreated patients with multisystem Langerhans' cell histiocytosis (LCH), vinblastine and etoposide were found to be equally effective treatments, showing similar response rates and survival probabilities after 24 weeks of treatment.

A lack of rapid response (within 6 weeks) to treatment was identified as a new prognostic indicator, indicating a higher risk of mortality, particularly in patients with risk organ involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. Gadner, H., Grois, N., Arico, M., et al.[2022]

Both the vindesine and prednisone (VP) regimen and the cyclophosphamide, etoposide, vindesine, and prednisone (CEVP) regimen showed similar efficacy in treating adult Langerhans cell histiocytosis, with non-active disease rates of approximately 70% for both groups.

However, the CEVP regimen was associated with a significantly higher rate of neutropenia (48.4%) compared to the VP regimen (7.1%), indicating a potential safety concern with the more intensive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of vindesine and prednisone and cyclophosphamide, etoposide, vindesine, and prednisone as first-line treatment for adult Langerhans cell histiocytosis: A single-center retrospective study. Duan, MH., Han, X., Li, J., et al.[2016]

Allogeneic bone marrow transplantation (BMT) using a total body irradiation (TBI)-containing regimen was effective in treating five children with Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis, with four patients surviving disease-free for a median of 63 months after treatment.

The study found no cases of acute or chronic graft-versus-host disease (GvHD) among the patients, suggesting that the TBI-based conditioning regimen is safe and well-tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen. Hale, GA., Bowman, LC., Woodard, JP., et al.[2007]

In a study of 83 children with histiocytosis X, three treatment regimens (vinblastine alone, vinblastine with prednisone, and vinblastine with prednisone and 6-mercaptopurine) showed similar effectiveness in managing the disease.

Despite the high mortality rate often associated with histiocytosis X, 71% of the patients (59 out of 83) are currently alive, indicating a positive outcome for these treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histiocytosis X--comparison of three treatment regimens. Lahey, ME.[2019]

In a study involving over 400 patients with multisystem LCH, prolonged treatment led to significantly improved 5-year survival rates (84%) and lower reactivation rates (27%) compared to previous trials, indicating a more effective approach for high-risk patients.

For low-risk patients, extending treatment duration from 6 to 12 months resulted in significantly lower reactivation rates (37% vs. 54%), suggesting that longer treatment can enhance outcomes for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Gadner, H., Minkov, M., Grois, N., et al.[2022]

The combination chemotherapy of cyclophosphamide, vincristine, prednisone, and procarbazine resulted in a 38% response rate in patients with histiocytosis X, which was not better than the response rates achieved with the individual drugs alone.

This study reinforces previous findings that combining these effective agents does not enhance treatment outcomes for histiocytosis patients, particularly those with poor prognostic indicators, unlike the improved response seen in Hodgkin's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a MOPP-type regimen in histiocytosis X--a Southwest Oncology Group study. Komp, DM., Silva-Sosa, M., Miale, T., et al.[2015]

The study discusses three cases of histiocytosis X treated over six years using a combination of vinblastine and prednisone, suggesting a long-term treatment approach.

Vinblastine was administered at doses of 0.1-0.3 mg/kg/day weekly, alongside prednisone at 20 mg every 48 hours, indicating a specific dosing regimen for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Histiocytosis X. Three cases treated with prednisone and vinblastine (author's transl)]. Escobar, H., Suárez, L.[2013]

Standard treatment for Langerhans cell histiocytosis typically involves vinblastine and prednisone, with additional medications like methotrexate or mercaptopurine based on disease severity.

For patients who do not respond to standard therapies, options like cytosine arabinoside and cladribine are effective, and emerging treatments include monoclonal antibodies targeting specific markers on Langerhans cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug therapy for the treatment of Langerhans cell histiocytosis. McClain, KL.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8822720/

Intermediate-dose cytarabine is an effective therapy for adults ... We found that cytarabine has favourable clinical efficacy in non-Langerhans cell histiocytosis patients with multisystem involvement regardless ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38018049/

[Efficacy and safety of intermediate-dose cytarabine in the ... The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year ...

3. journals.lww.com journals.lww.com/jaht/fulltext/2021/12040/efficacy_of_single_agent_cytarabine_in_adult.8.aspx

Efficacy of Single-Agent Cytarabine in Adult Langerhans... Single agent cytarabine appears safe and effective for adult patients with LCH. We provide a short summary of available data.

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/study/NCT04773366

NCT04773366 | A Prospective Study for the Treatment of ... In this study, we administer a cytarabine contained protocol to patients with multisystem involvement with or without risk organs involvement. The treatment ...

5. ashpublications.org ashpublications.org/blood/article/126/12/1415/34387/Cladribine-and-cytarabine-in-refractory

Cladribine and cytarabine in refractory multisystem ... The overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%). Thus, the combination of cladribine/Ara-C is effective therapy ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11214602/

Langerhans Cell Histiocytosis: NACHO Update on Progress ... Cytarabine (100–170 mg/m2/day) × 5 days every 4 weeks for 6–12 months. 3 month 3 year 3 year, ORR – 59% PFS-41% OS-100%. Intermediate ( ...

7. researchgate.net researchgate.net/publication/378400242_Phase_2_study_using_low_dose_cytarabine_for_adult_patients_with_newly_diagnosed_Langerhans_cell_histiocytosis

Phase 2 study using low dose cytarabine for adult patients ... The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3- ...

8. ashpublications.org ashpublications.org/hematology/article/2023/1/386/506404/Langerhans-cell-histiocytosis-promises-and-caveats

Langerhans cell histiocytosis: promises and caveats of ... Clofarabine (25 mg/m2/d, 5 days/cycle, for 6 cycles) is also promising, with 1-year PFS of 76% in 11 multiply refractory patients and minimal ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/bjh.19903

Methotrexate and cytarabine in adult LCH: High risk ... After a median follow-up of 78 months, the overall response, 6-year event-free survival and 6-year overall survival rates were 89.5%, 55% and 93 ...