Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis

NCT00618540 | Terminated Phase 2 Results DMC

• 4 other identifiers: 2007UC002UMN-0612M98407LCH-HCT-2006UMN-MT2006-07
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and melphalan followed by a donor stem cell transplant works in treating young patients with resistant Langerhans cell histiocytosis.

Conditions

Histiocytosis, Langerhans-cell

Keywords

childhood Langerhans cell histiocytosis

Outcome Measures

Primary Outcomes (2)

• Overall Survival

  Count of patients alive at 1 and 3 years. Deaths from any cause are events. Surviving patients are censored at the date of last contact.

  Year 1, Year 3

• Disease-free Survival at 12 Months Post Transplantation

  This outcome is defined as survival with resolution of LCH at 12 months post transplant. Unresolved disease for over 12 months post-transplant, progressive disease after this time period, recurrence of disease and death from any cause are considered events. Those who survive with resolution of disease are censored at the date of last contact.

  Year 1

Secondary Outcomes (6)

• Transplantation-related Death

  Day 100

• Neutrophil Engraftment

  Day 100

• Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)

  Day 100 and Month 6

• Incidence of Chronic GVHD

  Day 100 and Month 6

• Platelet Engraftment

  Day 100

Study Arms (1)

Alemtuzumab

EXPERIMENTAL

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

Biological: alemtuzumab; Drug: fludarabine phosphate; Drug: melphalan; Procedure: stem cell transplantation

Interventions

alemtuzumab BIOLOGICAL

Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

Also known as: Campath(R)

Alemtuzumab

fludarabine phosphate DRUG

Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3. (dose adjust if age \<12 months)

Also known as: Fludara(R)

Alemtuzumab

melphalan DRUG

Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age \<12 months)

Also known as: Alkeran

Alemtuzumab

stem cell transplantation PROCEDURE

Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Also known as: Stem cell transplant

Alemtuzumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed Langerhans cell histiocytosis (LCH) by demonstration of CD1a positivity or Birbeck granules in lesions
• Considered poor-risk, defined as multisystem disease with involvement of one or more risk organs (i.e., liver, spleen, lungs, and/or hematopoietic system)
• No isolated "lung only" LCH
• Progressive disease after one of the following treatments:
• LCH-III protocol or other standard LCH-directed therapies
• At least 1 course of the current salvage protocol (i.e., LCH-2 2005) or similar therapy (e.g., cytosine arabinoside or cladribine-based regimens)
• HLA-matched related or unrelated donor OR unrelated umbilical cord blood (UCB) available
• locus mismatch for donor allowed
• Up to 2 loci mismatch for unrelated UCB allowed
• Any hematologic status (transfusion support allowed)
• Adequate hepatic, renal, cardiac, and pulmonary function to undergo reduced-intensity hematopoietic cell transplantation (RI-HCT) including the following:
• Transaminases \< 5 times upper limit of normal (ULN)
• Bilirubin \< 3 times ULN (unless secondary to hepatic LCH)
• Creatinine ≤ 2 mg/dL (adults) (if creatinine \> 1.2 OR history of renal dysfunction, must have estimated creatinine clearance \> 40 mL/min)
• Creatinine clearance \> 40 mL/min (pediatrics)

You may not qualify if:

• Decompensated congestive heart failure, uncontrolled arrhythmia, or left ventricular ejection fraction ≥ 35%
• Pulmonary failure (i.e., requiring mechanical ventilation) unless secondary to active underlying LCH
• Isolated liver sclerosis or pulmonary fibrosis unless secondary to active underlying LCH
• Uncontrolled active life-threatening infection
• Pregnant or nursing
• Less than 4 weeks after last attempted salvage chemotherapy treatment
• Other concurrent chemotherapy agents (e.g., methotrexate) during entire transplantation period up to day 100 post-transplantation

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell

Interventions

Alemtuzumab; fludarabine phosphate; Melphalan; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Angela Smith, MD
• Organization: University of Minnesota, Pediatric BMT

smith719@umn.edu

612-626-2778

Study Officials

• Angela Smith

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2008
• First Posted: February 20, 2008
• Study Start: January 1, 2007
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: December 28, 2017
• Results First Posted: November 3, 2015

Record last verified: 2017-12

Locations

US (1)