Clofarabine for Langerhans Cell Histiocytosis

Not currently recruiting at 14 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called clofarabine to determine its effectiveness in treating Langerhans Cell Histiocytosis (LCH) and related disorders. The goal is to assist those who haven't succeeded with previous treatments. Participants will receive clofarabine through an IV for a set number of cycles. Suitable candidates include individuals with LCH or similar conditions who have not responded to treatments like chemotherapy or specific drugs. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that clofarabine is likely to be safe for humans?

Research has shown that clofarabine has been used in other studies to treat certain blood cancers. In these studies, patients generally tolerated clofarabine well. Common side effects included nausea, fever, and infections, but these were usually manageable with care.

Detailed safety data for clofarabine in treating Langerhans Cell Histiocytosis (LCH) is not yet available, but its presence in this trial phase indicates some evidence of safety in humans. This suggests the treatment might be reasonably safe, though risks may still exist.

If clofarabine is already approved for other uses, it indicates some level of safety, though effects can vary depending on the condition treated. Participants should always discuss potential risks and side effects with healthcare providers before joining any trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Langerhans Cell Histiocytosis?

Clofarabine is unique because it offers a different approach for treating Langerhans Cell Histiocytosis (LCH) and related disorders compared to the typical use of corticosteroids and chemotherapy regimens. Unlike standard treatments, Clofarabine is a purine nucleoside analog that disrupts DNA synthesis in cancer cells, potentially leading to more effective cancer cell death. Researchers are excited about Clofarabine because it targets rapidly dividing cells, which might make it more effective for patients with recurrent or refractory LCH who have not responded well to other therapies. Additionally, its administration via IV over a short 5-day cycle could offer a quicker intervention compared to some longer chemotherapy schedules.

What evidence suggests that clofarabine might be an effective treatment for Langerhans Cell Histiocytosis?

This trial will evaluate Clofarabine as a treatment for Langerhans Cell Histiocytosis (LCH) and related disorders. Participants with recurrent or refractory LCH will receive Clofarabine, which has shown promise in patients unresponsive to previous chemotherapy. Clofarabine attacks the DNA of abnormal cells, halting their growth and causing cell death. Participants with related conditions like Rosai-Dorfman Disease (RDD) and Erdheim-Chester Disease (ECD) will also receive Clofarabine, particularly when other treatments have failed. Overall, this trial studies Clofarabine as a potential treatment option for these challenging conditions. ^{3 6 7 8 9}

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

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.

Provide signed written informed consent

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10615682/

Outcomes after interruption of targeted therapy in patients ... MEK inhibitors have demonstrated efficacy across histiocytic neoplasms (i.e. Langerhans cell histocytosis [LCH], Rosai-Dorfman Disease [RDD] and juvenile ...

2. jaadcasereports.org jaadcasereports.org/article/S2352-5126(25)00079-7/fulltext

Mixed histiocytosis of Langerhans cell with Rosai-Dorfman ... Histiocytoses are a group of rare proliferative disorders that share a common CD34+ progenitor cell in the bone marrow.

3. ctv.veeva.com ctv.veeva.com/study/study-of-clofarabine-in-patients-with-recurrent-or-refractory-langerhans-cell-histiocytosis-and-lch

Study of Clofarabine in Patients With Recurrent or Refractory ... This research study is evaluating a drug called clofarabine as a possible treatment for Langerhans Cell Histiocytosis (LCH) and and other ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0024320524002820

Advances in Understanding and Management of Erdheim ... Erdheim Chester Disease (ECD) is a rare histiocytic disorder marked by infiltration of organs with CD68 + histiocytes.

5. ashpublications.org ashpublications.org/hematology/article/2020/1/395/474332/Histiocytic-disorders-insights-into-novel-biology

Histiocytic disorders: insights into novel biology and ... Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are caused by mutations of the MAPK pathway, most often BRAFV 600E, in myeloid dendritic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02425904

NCT02425904 | Study of Clofarabine in Patients With ... This research study is evaluating a drug called clofarabine as a possible treatment for Langerhans Cell Histiocytosis (LCH) and and other histiocytic disorders.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7434330/

Highlights of the Management of Adult Histiocytic Disorders This document will provide highlights for management of the most commonly encountered histiocytic diseases (Langerhans cell histiocytosis, ...

8. mayoclinicproceedings.org mayoclinicproceedings.org/article/S0025-6196(19)30273-3/fulltext

Erdheim-Chester Disease, Langerhans Cell Histiocytosis ... ... Chester Disease, Langerhans Cell Histiocytosis ... Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease.

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

Langerhans cell histiocytosis: promises and caveats of ... Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm driven by activating mutations in the MAPK pathway, most commonly BRAF-V600E and MAP2K1.