Clofarabine for Langerhans Cell Histiocytosis

Recruiting at 13 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Investigational agents, Renal toxic drugs

Disqualifiers: Chemotherapy, Radiotherapy, Uncontrolled illness, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5.5-7 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This research study is evaluating a drug called clofarabine as a possible treatment for Langerhans Cell Histiocytosis (LCH) and and other histiocytic disorders.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention avoiding drugs with known kidney toxicity during clofarabine treatment and not using alternative medications like herbal supplements. It's best to discuss your current medications with the study team.

Is clofarabine safe for treating Langerhans Cell Histiocytosis?

Clofarabine has been used in children with refractory Langerhans Cell Histiocytosis and showed minimal toxicity, suggesting it is generally safe for this condition. ^{1 2 3 4 5}

How is the drug clofarabine unique in treating Langerhans Cell Histiocytosis?

Clofarabine is unique in treating Langerhans Cell Histiocytosis because it has shown significant activity as a single agent in patients with refractory forms of the disease, offering a potential option with minimal toxicity compared to other aggressive treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Clofarabine for treating Langerhans Cell Histiocytosis?

Clofarabine has shown effectiveness in treating various blood cancers, such as acute lymphoblastic leukemia and acute myeloid leukemia, and has been approved for pediatric use in relapsed cases. While there is no direct evidence for Langerhans Cell Histiocytosis, its success in similar conditions suggests potential effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Barbara Degar, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for people of all ages with active Langerhans Cell Histiocytosis (LCH) or related disorders, who have tried at least one treatment before. They must not be pregnant, breastfeeding, or have had certain other cancers within the last 5 years. Participants need to have a performance score above 70%, normal kidney and liver function tests, and can't be on drugs that could harm their kidneys during the study.

Inclusion Criteria

Provide signed written informed consent

For stratum 1, you have tried one type of chemotherapy in the past and it didn't work. For stratum 2, if you have RDD, you have tried corticosteroid treatment and it didn't work. If you have ECD with a specific gene mutation, you have tried a certain medication and it didn't work, or you are not eligible for that treatment.

Your liver enzyme levels are not too high, unless it's due to a specific condition called LCH.

Exclusion Criteria

I am not taking kidney-harming drugs during my clofarabine treatment.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am not using any herbal or alternative medicines that could affect the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Clofarabine administered via IV on days 1-5, 25 mg/m2/day per cycle for 2 cycles. If no disease progression, continue with same dose for maintenance treatment for 4 additional cycles.

5.5-7 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Clofarabine

Trial Overview The drug being tested is clofarabine for treating LCH and similar conditions. The study will look at how well it works in patients who've already tried other treatments without success. It's given under controlled conditions to monitor its effectiveness and safety.

How Is the Trial Designed?

Group I: Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine Experimental Treatment 1 Intervention

Participants with recurrent or refractory LCH defined as with multi-focal or multi-system disease who have recurred (or have refractory disease) after at least one prior systemic chemotherapy regimen. Patient will receive Clofarabine administered via IV on days 1-5, 25 mg/m2/day per cycle for 2 cycles. At the end of cycle 2 if no disease progression, will continue with same dose for maintenance treatment for 4 additional cycles.

Group II: LCH-related disorders + Clofarabine Experimental Treatment 1 Intervention

Participants with LCH-related disorders defined as who require systemic chemotherapy including participants with Rosai Dorfman Disease (RDD) who have not responded to or recurred after treatment with corticosteroids. Erdheim Chester Disease (ECD) subjects who have confirmed presence of BRAF V600E mutation must have not responded to, have recurred after, or be unable to receive treatment with a BRAF inhibitor. Patient will receive Clofarabine administered via IV on days 1-5, 25 mg/m2/day per cycle for 2 cycles. At the end of cycle 2 if no disease progression, will continue with same dose for maintenance treatment for 4 additional cycles.

Clofarabine is already approved in United States, European Union for the following indications:

Approved in United States as Clolar for:

• Acute lymphoblastic leukemia (ALL) in pediatric patients

Approved in European Union as Evoltra for:

• Acute lymphoblastic leukemia (ALL) in pediatric patients

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

St. Baldrick's Foundation

Collaborator

Trials

19

Recruited

9,100+

Cookies for Kids' Cancer

Collaborator

Trials

7

Recruited

360+

North American Consortium for Histiocytosis

Collaborator

Trials

5

Recruited

1,700+

Published Research Related to This Trial

Clofarabine is a nucleoside analog effective for treating pediatric relapsed or refractory acute lymphoblastic leukemia, with pharmacokinetics showing rapid absorption and a bioavailability of 57.5%.

The pharmacokinetics of clofarabine differ significantly between adults and children, with adults experiencing higher drug exposure at similar doses, indicating that dose adjustments may be necessary for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of clofarabine and its metabolite 6-ketoclofarabine in adult and pediatric patients with cancer. Bonate, PL., Cunningham, CC., Gaynon, P., et al.[2018]

Clofarabine is an effective treatment for hematologic malignancies, including acute lymphoblastic leukemia and acute myeloid leukemia, and is already approved for use in pediatric patients after two prior therapies.

Clinical trials indicate that clofarabine works well both alone and in combination with other drugs for adult myeloid leukemia, showing promise particularly in older patients and those with challenging genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clofarabine: a new treatment option for patients with acute myeloid leukemia. Larson, ML., Venugopal, P.[2018]

In a study of seven male patients with multisystem or multifocal Langerhans cell histiocytosis, cladribine treatment led to clinically significant responses in all patients, with 86% achieving durable complete remissions over a median follow-up of 37 months.

Cladribine demonstrated a favorable safety profile, with the most common side effects being transient bone marrow suppression, including grade 3 lymphopenia in 71% of patients, indicating it is a viable frontline therapy for this rare condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cladribine (2-chlorodeoxyadenosine) in frontline chemotherapy for adult Langerhans cell histiocytosis: A single-center study of seven cases. Adam, Z., Szturz, P., Vaníček, J., et al.[2013]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of clofarabine and its metabolite 6-ketoclofarabine in adult and pediatric patients with cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Clofarabine. [2018]

3. England pubmed.ncbi.nlm.nih.gov

A Phase I Dose-Escalation Study of Clofarabine in Patients with Relapsed or Refractory Low-Grade or Intermediate-Grade B-Cell or T-Cell Lymphoma. [2019]

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

Immune Thrombocytopenia in a Child With Refractory Langerhans Cell Histiocytosis Following Cladribine Containing Therapy. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Clofarabine: a new treatment option for patients with acute myeloid leukemia. [2018]

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

Clofarabine in refractory Langerhans cell histiocytosis. [2022]

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

Clofarabine salvage therapy for refractory high-risk langerhans cell histiocytosis. [2018]

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

Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Cladribine (2-chlorodeoxyadenosine) in frontline chemotherapy for adult Langerhans cell histiocytosis: A single-center study of seven cases. [2013]

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

Mixed Langerhans Cell Histiocytosis and Erdheim-Chester Disease in a Girl: A Rare and Puzzling Diagnosis. [2021]