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

Trial Summary

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.

What data supports the effectiveness of the drug combination Vinblastine/Prednisone vs. Cytarabine for treating histiocytosis?

Research shows that vinblastine and prednisone, when used together, have been effective in treating multisystem Langerhans cell histiocytosis, with a 5-year survival rate of 84% in high-risk patients. This suggests that the combination can be beneficial for similar histiocytic disorders. ^{1 2 3 4 5}

Is the combination of Vinblastine and Prednisone safe for treating histiocytosis?

The combination of Vinblastine and Prednisone has been used in treating Langerhans cell histiocytosis, with studies showing it is generally safe for patients, as many have survived the treatment. However, specific safety details for each drug combination are not provided in the available research. ^{1 4 5 6 7}

How is the drug combination of Vinblastine, Prednisone, and Cytarabine unique for treating histiocytosis?

This drug combination is unique because it combines Vinblastine and Prednisone, which are commonly used in treating histiocytosis, with Cytarabine, a drug typically used for leukemia, potentially offering a novel approach by targeting the disease with a different mechanism of action. ^{1 2 4 5 8}

What is the purpose of this trial?

Langerhans Cell Histiocytosis (LCH) is a type of cancer that can damage tissue or cause lesions to form in one or more places in the body. Langerhans cell histiocytosis (LCH) is a cancer that begins in LCH cells (a type of dendritic cell which fights infection). Sometimes there are mutations (changes) in LCH cells as they form. These include mutations of the BRAF gene. These changes may make the LCH cells grow and multiply quickly. This causes LCH cells to build up in certain parts of the body, where they can damage tissue or form lesions. For most patients with LCH, standard-of-care vinblastine/prednisone are used as front-line therapy while cytarabine therapy has been used as therapy for patients who develop recurrence. No alternate treatment strategy has been developed for frontline therapy in LCH. The purpose of this research study is to compare previously used vinblastine/prednisone to single therapy with cytarabine for LCH. We will evaluate the utility of an imaging study called a positron emission tomography (PET) scan to more accurately assess areas of LCH involvement not otherwise seen in other imaging studies as well as response to therapy. We also want to identify if genetic and other biomarkers (special proteins in patient's blood and in patient's cancer) relate to the response of patients LCH to study treatment.

Research Team

Olive Eckstein, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

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

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

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

Evaluation of a MOPP-type regimen in histiocytosis X--a Southwest Oncology Group study. [2015]

3. England 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. [2007]

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

Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. [2022]

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

A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. [2022]

6. England 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. [2016]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Spain pubmed.ncbi.nlm.nih.gov

[Histiocytosis X. Three cases treated with prednisone and vinblastine (author's transl)]. [2013]