Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis

NCT02385110 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0989NCI-2015-00526
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to compare the effect of adding either alemtuzumab or tocilizumab to the drug combination of etoposide and dexamethasone in controlling HLH. The safety of the drug combinations will also be studied. This is an investigational study. Alemtuzumab, etoposide, tocilizumab, and dexamethasone are not FDA approved for the treatment of HLH. Etoposide is FDA approved and commercially available for the treatment of testicular cancer and lung cancer. Alemtuzumab is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia. Dexamethasone is a steroid used to reduce inflammation. Tocilizumab is FDA approved and commercially available for the treatment of arthritis. The combination of alemtuzumab, etoposide, tocilizumab, and dexamethasone to treat HLH is investigational. The study doctor can explain how the drugs are designed to work. Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.

Conditions

Leukemia

Keywords

Leukemia; Hemophagocytic lymphohistiocytosis; HLH; Alemtuzumab; CAMPATH-1H; Campath; Etoposide; VePesid; Dexamethasone; Decadron; Methotrexate; Phone call

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Response to Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis

  Response is defined as complete response (CR) and/or partial response (PR) and/or parameter improvements (PI). Complete response (CR) is normalization to within institutional normal limits of diagnostic clinical and laboratory abnormalities associated with HLH. In the case of ferritin, normalization OR a 3 fold improvement in the pre-study level will be evidence of complete response, provided the post therapy level is also below 10000 ng/ml. Partial response (PR) is sustained normalization of 3 or more of the diagnostic clinical and laboratory abnormalities noted above (or, with ferritin, improvement as described above) and no apparent progression of other aspects of disease pathology. Parameter improvements (PI) is at least a 25% improvement in two or more quantifiable symptoms and/or laboratory markers from those mentioned above within 8 weeks (+/- 7 days) of initiation of therapy.

  8 weeks

• Disease Free Survival

  Time from date of treatment start until the date of first objective documentation of disease-relapse.

  8 weeks

Study Arms (2)

Group 1: Alemtuzumab + Etoposide + Dexamethasone

EXPERIMENTAL

Induction Phase: Participants receive Alemtuzumab daily on Days 1 - 4 with weekly Etoposide, and Dexamethasone by vein on Days 1-7 during the 8-weeks. Participants with central nervous system involvement receive intrathecal methotrexate 12 mg once a week for 5 weeks. Dexamethasone by vein on Days 1-7 of the induction phase. Maintenance Phase: Starts Post Induction Phase for16 weeks. Participants receive Alemtuzumab once every 4 weeks and Dexamethasone three times per week. Participants who have evidence of budding relapse may revert back to receiving Etoposide. If participant responds to study drugs, they will receive a phone call by study staff every 3 - 6 months for up to 5 years after completion of treatment. Each call will last about 5-10 minutes.

Drug: Alemtuzumab; Drug: Etoposide; Drug: Dexamethasone; Drug: Methotrexate; Behavioral: Phone Call

Group 2: Etoposide + Dexamethasone + Tocilizumab

EXPERIMENTAL

Induction Phase: Participants receive Tocilizumab by vein over 60 minutes on Day 1 or Day 2. Participants receive Alemtuzumab daily on Days 1 - 4 with weekly Etoposide and Dexamethasone by vein on Days 1-7 during the 8-weeks. Participants with central nervous system involvement receive intrathecal methotrexate 12 mg once a week for 5 weeks. Maintenance Phase: Starts Post Induction Phase and will last 16 weeks. Tocilizumab not given in the Maintenance Phase. Dexamethasone three times per week. If participant responds to study drugs, they will receive a phone call by study staff every 3 - 6 months for up to 5 years after completion of treatment. Each call will last about 5-10 minutes

Drug: Alemtuzumab; Drug: Etoposide; Drug: Dexamethasone; Drug: Methotrexate; Behavioral: Phone Call; Drug: Tocilizumab

Interventions

Alemtuzumab DRUG

Group 1 and 2 Induction Phase: Alemtuzumab total dose of 1.0 mg/kg subcutaneously or by vein over 4 days (days 1-4) during the 8 week induction phase. Day 1 0.1 mg/kg, Day 2 0.3 mg/kg, Day 3 0.3 mg/kg, Day 4 0.3 mg/kg. Group 1 Maintenance Phase: 0.2 mg/kg once every 4 weeks for 6 weeks.

Also known as: CAMPATH-1H, Campath

Group 1: Alemtuzumab + Etoposide + Dexamethasone; Group 2: Etoposide + Dexamethasone + Tocilizumab

Etoposide DRUG

Induction Phase: 150 mg/m2 given by vein once a week for 8 weeks. Maintenance Phase: Participants who have evidence of refractory disease or budding relapse during the maintenance phase may revert back to receiving Etoposide.

Also known as: VePesid

Group 1: Alemtuzumab + Etoposide + Dexamethasone; Group 2: Etoposide + Dexamethasone + Tocilizumab

Dexamethasone DRUG

Induction Phase: 10 mg/m2 for 1 week followed by Dexamethasone 5 mg/m2 for 2 weeks followed by Dexamethasone 2.5 mg/m2 for 2 weeks followed by Dexamethasone 1.25 mg/m2 for 2 weeks. Maintenance Phase: 1.25 mg/m2 by mouth three times a week for 16 weeks.

Also known as: Decadron

Group 1: Alemtuzumab + Etoposide + Dexamethasone; Group 2: Etoposide + Dexamethasone + Tocilizumab

Methotrexate DRUG

Participants with central nervous system involvement receive intrathecal methotrexate 12 mg once a week for 5 weeks during the Induction Phase.

Group 1: Alemtuzumab + Etoposide + Dexamethasone; Group 2: Etoposide + Dexamethasone + Tocilizumab

Phone Call BEHAVIORAL

If participant responds to study drugs, they will receive a phone call by study staff every 3 - 6 months for up to 5 years after completion of treatment. Each call will last about 5-10 minutes.

Group 1: Alemtuzumab + Etoposide + Dexamethasone; Group 2: Etoposide + Dexamethasone + Tocilizumab

Tocilizumab DRUG

Induction Phase: Tocilizumab at 4 to 8 mg/kg by vein. Day 1 0.1 mg/kg,Day 2 0.3 mg/kg, Day 3 0.3 mg/kg, Day 4 0.3 mg/kg.

Group 2: Etoposide + Dexamethasone + Tocilizumab

Eligibility Criteria

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

You may qualify if:

• Sign an IRB-approved informed consent document.
• Patients must be \>/= 18 years of age.
• A documentation of diagnosis of hemophagocytic lymphocytosis, either newly diagnosed or relapsed/refractory by the treating physician and the PI in the patients chart. It must be noted that no diagnostic criteria have been established for diagnosis of HLH in adult patients as this was a hitherto poorly identified and considered to be a very rare disease in adults. We have seen an increasing number of cases of HLH at our institution over the last 2 years partly due to referrals and partly due to better understanding of the disease through discussions with our collaborators Dr Kenneth McClain and Dr Carl Allen at TCH (experts in pediatric HLH). Adult HLH seems to occur more frequently post malignancy and has a more fulminant course than pediatric HLH.
• Continued from No. 3: The diagnostic criteria that have been traditionally used for children (HLH 1991 and HLH 2004) may not adequately diagnose HLH in adults. This is the first adult HLH protocol in the country. In the absence of standard diagnostic guidelines if the patient's symptoms are highly suspicious for HLH and after an adequate work-up to rule out alternate potential alternate etiologies is performed we will treat the patient for HLH as missing the diagnosis is associated with high mortality. These patients will be discussed with the PI (Dr Daver) prior to enrollment in all such cases.
• Organ function as defined below (unless due to the HLH process): Serum creatinine \</= 3.0 mg/dL, Total bilirubin \</= 5.0 mg/dL. If organ dysfunction is thought to be related to the HLH process this must be clearly documented in the chart and the patients may be enrolled on study irrespective of creatinine and bilirubin levels.
• Women of childbearing potential must practice contraception. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, prior to study entry and for at least 3 months after the last dose of study drug.
• Negative urine pregnancy test and/or serum pregnancy test within 7 days of initiation of therapy.
• Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, prior to study entry and for at least 3 months after the last dose of study drug.

You may not qualify if:

• Pregnant and breast feeding women
• Any serious/and or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
• Patients unwilling or unable to comply with the protocol.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia; Lymphohistiocytosis, Hemophagocytic

Interventions

Alemtuzumab; Etoposide; Dexamethasone; Calcium Dobesilate; Methotrexate; tocilizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Naval Daver, MD./Professor
• Organization: The University of Texas MD Anderson Cancer Center

NDaver@mdanderson.org

713-794-4392

Study Officials

• Naval Daver, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 11, 2015
• Study Start: September 23, 2015
• Primary Completion: January 24, 2023
• Study Completion: January 24, 2023
• Last Updated: January 17, 2024
• Results First Posted: January 17, 2024

Record last verified: 2023-12

Locations

US (1)