Chemotherapy With or Without Radiation, Low and Intermediate Risk Hodgkins Lymphoma, TXCH-HD-12A

NCT01858922 | Completed Phase 2 DMC

• 2 other identifiers: H-30993 TXCH-HD-12ATXCH-HD-12A
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Subjects have a type of cancer called Hodgkin Disease (HD), a cancer of the lymph system. The lymph system is made up of tissue throughout the body that makes and stores infection-fighting cells. HD is one of the most treatable childhood cancers. The standard treatment for HD involves chemotherapy (treatment with anti-cancer drugs) and radiation therapy (the use of high-dose x-rays to get rid of cancer cells). Although they are cured from their cancer, some patients experience negative side effects from treatment later in life. These kinds of side effects are often referred to as late effects. This can include problems with growth, problems with some organ functions, and sometimes second cancers. These types of effects can be associated with either chemotherapy or radiation therapy. The investigators are therefore designing studies to minimize or prevent these late effects. It is thought that if some patients can be successfully treated without radiation, those patients might experience fewer late side effects. Some patients, however, do not respond as well to the first stages of treatment (slow early responders). Slow early responders are considered to be at higher risk for relapse. This study also looks at whether these kinds of patients will benefit from additional chemotherapy. The purpose of this study is to look at how the immune system recovers and at how certain T-cells in the blood behave after receiving chemotherapy with or without radiation. The investigators also want to identify if bio-markers (special proteins in blood and in cancer) relate to the response of HD to study treatment.

Conditions

Hodgkin Disease

Keywords

Hodgkin's Lymphoma; ABVE-PC; doxorubicin; bleomycin; vincristine; etoposide; prednisone; cyclophosphamide; DECA; decadron; cisplatin; cytarabine; Radiation

Outcome Measures

Primary Outcomes (6)

• Response to therapy from Day 1 of Treatment

  To define the general immune recovery in patients with low and intermediate risk HD undergoing chemotherapy with or without radiation therapy. Descriptive analysis of response to therapy, event-free survival, overall survival, relapse, and infection will be summarized using summary statistics.

  up to 18 months

• Changes in Frequency of Regulatory Cell Population

  To identify the behavior of antigen-specific cytotoxic T-cells and specific chemokine/cytokine biomarkers in patients with low and intermediate risk HD who receive chemotherapy with or without radiation therapy using means, medians, standard deviations, and confidence interval estimates. Pairwise comparisons, paired t-tests, and/or Wilcoxon signed-rank tests will be used to compare the changes.

  Baseline and 3 Months

• Changes in Frequency of Regulatory Cell Population

  To identify the behavior of antigen-specific cytotoxic T-cells and specific chemokine/cytokine biomarkers in patients with low and intermediate risk HD undergoing chemotherapy with or without radiation therapy will be analyzed using means, medians, standard deviations, and confidence interval estimates. Pairwise comparisons, paired t-tests, and/or Wilcoxon signed-rank tests will be used to compare the changes.

  Baseline to 6 months

• Changes in Frequency of Regulatory Cell Population

  To identify the behavior of antigen-specific cytotoxic T-cells and specific chemokine/cytokine biomarkers in patients with low and intermediate risk HD undergoing chemotherapy with or without radiation therapy will be analyzed using means, medians, standard deviations, and confidence interval estimates. Pairwise comparisons, paired t-tests, and/or Wilcoxon signed-rank tests will be used to compare the changes.

  Baseline to 12 Months

• Changes in Frequency of Regulatory Cell Population

  To identify the behavior of antigen-specific cytotoxic T-cells and specific chemokine/cytokine biomarkers in patients with low and intermediate risk HD undergoing chemotherapy with or without radiation therapy will be analyzed using means, medians, standard deviations, and confidence interval estimates. Pairwise comparisons, paired t-tests, and/or Wilcoxon signed-rank tests will be used to compare the changes.

  Baseline to 18 Months

• Function of Regulatory Cell Population

  To identify tumor and circulating biomarkers in patients with low and intermediate risk HD who receive chemotherapy with or without radiation therapy and correlate with clinical outcomes including incidence of relapse and infection using random coefficient mixed models and multivariate cox proportional hazard modeling.

  Up to 18 months

Study Arms (2)

Rapid Early Responders

EXPERIMENTAL

All patients will have initial treatment utilizing ABVE-PC x2 cycles. Those patients with rapid early response (RER) determined by FDG-PET/CT scan after two cycles of ABVE-PC will receive two more cycles of ABVE-PC. If subsequent PET/CT scan indicates a complete response (CR), therapy will stop and regular follow-up will begin. If the subsequent PET/CT for RER patients indicates a partial response, those patients will undergo IFRT.

Drug: ABVE-PC

Slow Early Responders

EXPERIMENTAL

All patients will have initial treatment utilizing ABVE-PC x2 cycles. Those patients determined to have a slow early response (SER) determined by PET/CT scan after two cycles of ABVE-PC will receive 2 courses of DECA. If after PET/CT, the patient has a partial or complete response, then 2 additional courses of ABVE-PC will be given. If subsequent PET/CT scan indicates PR or CR, those patients will then undergo IFRT. If stable or progressive disease is found at either PET/CT scan, the patient will be taken off-study and follow up will begin.

Drug: ABVE-PC; Drug: DECA

Interventions

ABVE-PC DRUG

Doxorubicin (A) 25mg/m2/day IV over 10min on Day 1 \& Day 2 Bleomycin (B) 5units/m2/day IV over 10min on Day 1 10units/m2/day IV over 10min on Day 8 Vincristine (V) 1.4mg/m2/day IV push with extravasation precautions on Day 1 \& 8 (Max dose 2.8mg) Etoposide (E) 125mg/m2/day IV over 1hr at a concentration of \</=0.4mg/ml in NS on Day 1, 2 \& 3 Prednisone (P) 40mg/m2/day PO divided in 2 doses every day on Day 1-7 IV equivalent of methylprednisolone is acceptable Cyclophosphamide (C) 800 mg/m2 IV over 1 hr in 200 ml/m2 NS on Day 1

Also known as: Doxorubicin (A), Bleomycin (B), Vincristine (V), Etoposide (E), Prednisone (P), Cyclophosphamide (C)

Rapid Early Responders; Slow Early Responders

DECA DRUG

Dexamethasone (D): 10 mg/m2 IV over 15 minutes on Day 1 and Day 2, prior to Etoposide/Cytarabine. Etoposide (E): 100 mg/m2 IV over 3 hours on Day 1 and Day 2 as continuous infusion mixed with cytarabine\* Cytarabine (A): 3000 mg/m2 IV over 3 hours on Day 1 and Day 2 as continuous infusion mixed with etoposide\* \*Mix together in NS at an etoposide concentration of \</=0.4 mg/ml Dexamethasone eyedrops: 2 drops in each eye 4 times a day on Day 1, Day 2, and Day 3. Cisplatin (C): 90 mg/m2 over 6 hours in 1000 ml/m2 NS + 10 gram/m2 mannitol on Day 1 as continuous infusion.

Also known as: Dexamethasone (D), Etoposide (E), Cytarabine (A), Cisplatin (C)

Slow Early Responders

Eligibility Criteria

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

You may qualify if:

• Patients with newly diagnosed, histologically confirmed Hodgkin Lymphoma (HD) who meet the following criteria:
• Stage IA and IB (non-bulky nodular lymphocyte predominant)
• Stage IIA and IIB
• Stage IIIA
• Stage IVA

You may not qualify if:

• Patients with Stage IA-IIA non-bulky lymphocyte predominant histology
• Patients who have received previous chemotherapy or radiation therapy (does NOT include steroids).
• Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction \<27%).
• Patients with severe renal disease (i.e. Measured or estimated creatinine clearance or radioisotope GFR \<= 70 ml/min/1.73 m2).
• Patients with pre-existing severe restrictive pulmonary disease (FVC less than 60% of predicted).
• Patients with severe hepatic disease (direct bilirubin greater than 3 mg/dl or AST greater than 500 IU/L).
• Known HIV positivity
• Patients with a Karnofsky performance score \<70% or Lansky score \<70%.
• Female patients who are pregnant or breast feeding.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Doxorubicin; Bleomycin; Vincristine; Etoposide; Prednisone; Cyclophosphamide; Dexamethasone; Fumigant 93; Cytarabine; Cisplatin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Steroids, Fluorinated; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Carl E. Allen, MD, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: May 21, 2013
• Study Start: December 19, 2012
• Primary Completion: August 12, 2019
• Study Completion: August 12, 2019
• Last Updated: January 12, 2024

Record last verified: 2024-01

Locations

US (1)