Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02425904
Recruitment Status : Active, not recruiting
First Posted : April 24, 2015
Last Update Posted : July 29, 2020
Sponsor:
Collaborators:
Sanofi
St. Baldrick's Foundation
Cookies for Kids' Cancer
North American Consortium for Histiocytosis
Information provided by (Responsible Party):
Barbara Degar, MD, Dana-Farber Cancer Institute

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

Condition or disease Intervention/treatment Phase
Langerhans Cell Histiocytosis Drug: Clofarabine Phase 2

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention, to learn whether the drug works in treating a specific disease, in this case, clofarabine to treat LCH.

"Investigational" means that the intervention is still being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved clofarabine for your disease.

Clofarabine is a chemotherapy drug that has been used and is approved by the FDA for the treatment of leukemia in children and adults. Information from other research studies suggests that this drug may also be effective in participants with LCH and other histiocytic disorders.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders
Actual Study Start Date : May 2015
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2025


Arm Intervention/treatment
Experimental: 1-Recurrent or Refractory LCH

Participants with multi-focal or multi-system disease who have recurred (or have refractory disease) after at least one prior systemic chemotherapy regimen.

  • Clofarabine administered via IV on days 1-5, 25 mg/m2/day, per cycle.
  • Evaluation of disease response will be performed after 2 cycles of Induction Therapy. In the absence of disease progression, participants will be eligible to receive up to 4 cycles of Maintenance Therapy, which is identical to the Induction Therapy.
Drug: Clofarabine
Evaluation of response to clofarabine
Other Names:
  • Clofarex
  • Clolar

Experimental: 2-LCH-related disorders

Participants with LCH-related disorders who require systemic chemotherapy including:

Participants with RDD who have not responded to or recurred after treatment with corticosteroids. 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.

  • Clofarabine administered via IV on days 1-5, 25 mg/m2/day, per cycle.
  • Evaluation of disease response will be performed after 2 cycles of Induction Therapy. In the absence of disease progression, participants will be eligible to receive up to 4 cycles of Maintenance Therapy, which is identical to the Induction Therapy.
Drug: Clofarabine
Evaluation of response to clofarabine
Other Names:
  • Clofarex
  • Clolar




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Week 7 ]
    Responses will be assessed using the standard criteria proposed by the Histiocyte Society


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: At three and five years ]
  2. Overall Survival [ Time Frame: At three and five years ]
  3. The proportion of patients who experience a toxicity-event requiring stopping clofarabine [ Time Frame: Baseline, Up to 24 weeks ]
  4. Proportion of participants with grade 3-4 toxicity [ Time Frame: Baseline, Up to 24 Weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Prior diagnosis of Langerhans Cell Histiocytosis (stratum 1) or LCH-related disorder (stratum 2) established by standard diagnostic criteria and confirmed histologically.
  • Evidence of active disease (histological confirmation of reactivation or progression is not required).
  • Performance Score > 70% (use Lansky score for age < 16 and Karnofsky score for age = >16).
  • Patients of all ages will be eligible.
  • Provide signed written informed consent.
  • In stratum 1, patients must have failed one prior systemic chemotherapy regimen. In stratum 2, RDD patients must have failed treatment with corticosteroid. ECD patients who have confirmed BRAF V600E mutation must have failed treatment with a BRAF inhibitor or are not considered to be eligible for such treatment.
  • There is no limitation of amount or the type of prior therapy or drugs.
  • Female patients of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
  • Participants must have adequate marrow functions as defined below, except those with involvement of hematopoietic system for whom these criteria can be waived:

    • Absolute neutrophil count ≥ 750 cells/µL
    • Platelets ≥75,000/µL
  • Participants must have adequate organ functions as defined below:

    • Total bilirubin ≤ 2.5x institutional upper limit of normal
    • AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal unless it is related to involvement by LCH
    • Adequate renal function defined as:
    • Pediatric Population (patients < 18 years): Creatinine within normal limits or calculated creatinine clearance greater than or equal to 90 ml/min/1.73 m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k x Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys.
    • Adult Population (patients >= 18 years): Serum creatinine less than or equal to 1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black), where serum creatinine is measured in mg/dL.
    • Alkaline phosphatase ≤ 2.5 x institutional upper limit of normal

Exclusion Criteria:

  • Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Corticosteroid treatment is allowed.
  • Participants may not be receiving any other investigational agents targeting Histiocytosis.
  • Clofarabine is excreted primarily by the kidneys. Therefore, drugs with known renal toxicity (e.g.vancomycin, amphotericin B, acyclovir, cyclosporin, methotrexate, tacrolimus) should be avoided to the extent possible during the 5 days of clofarabine treatment in each cycle or, if required, administered cautiously and with close monitoring.
  • Use of alternative medications (e.g., herbal or botanical that could interfere with clofarabine) is not permitted during the entire study period.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because clofarabine is a nucleoside analog with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with clofarabine, breastfeeding should be discontinued if the mother is treated with clofarabine. These potential risks may also apply to other agents used in this study.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
  • Patients with a history of prior hematopoietic stem cell transplantation (HSCT), elevated conjugated serum bilirubin at study entry, uncontrolled systemic fungal, bacterial, or other infection, a history of hepatitis B or C infection or a history of cirrhosis.
  • Individuals who are known to be HIV-positive on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with clofarabine. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02425904


Locations
Layout table for location information
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
University of California San Francisco Medical Center
San Francisco, California, United States, 94143
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
The Children's Hospital of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Dana-Farber Cancer Institute
Sanofi
St. Baldrick's Foundation
Cookies for Kids' Cancer
North American Consortium for Histiocytosis
Investigators
Layout table for investigator information
Principal Investigator: Barbara Degar, MD Dana-Farber Cancer Institute
Layout table for additonal information
Responsible Party: Barbara Degar, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02425904    
Other Study ID Numbers: 15-005
First Posted: April 24, 2015    Key Record Dates
Last Update Posted: July 29, 2020
Last Verified: July 2020
Keywords provided by Barbara Degar, MD, Dana-Farber Cancer Institute:
Langerhans Cell Histiocytosis
Additional relevant MeSH terms:
Layout table for MeSH terms
Histiocytosis, Langerhans-Cell
Histiocytosis
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Clofarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents