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Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17

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ClinicalTrials.gov Identifier: NCT03755804
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : July 11, 2019
Sponsor:
Collaborators:
Teva Pharmaceuticals USA
Seattle Genetics, Inc.
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date  ICMJE November 26, 2018
First Posted Date  ICMJE November 28, 2018
Last Update Posted Date July 11, 2019
Actual Study Start Date  ICMJE December 12, 2018
Estimated Primary Completion Date January 1, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
  • Response rate of adequate response [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment ]
    The 70 evaluable low-risk patients enrolled will be evaluated for this objective.
  • Response rate of adequate response [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment ]
    The 65 evaluable intermediate-risk patients enrolled will be evaluated for this objective
  • Event-free survival [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment ]
    Time to event defined as relapse, progression or death. The 65 evaluable high-risk patients participants enrolled will be evaluated for this objective.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03755804 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
  • Number of adverse events in low-risk and intermediate-risk patients [ Time Frame: From enrollment to end of therapy (approximately 8 months ]
    According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
  • Number of adverse events in high-risk patients [ Time Frame: From enrollment to end of therapy (approximately 8 months ]
    According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
  • Local failure rate [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment ]
    Local failure rate in irradiated and non-irradiated patients
  • Event-free survival [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment ]
    Time to event defined as relapse, progression or death. The EFS for the low-risk patients and intermediate-risk patients are compared to those in HOD08 and HOD05, respectively.
  • Response rate [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment ]
    Response rate of adequate response after 2 cycles of AEPA in the high-risk patients with FDG-PET compared to that after 2 cycles of AEPA in HLHR13.
  • Response rate [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment ]
    Response rate of adequate response after 2 cycles of BEABOVP in the low-risk and high-risk patients with FDG-PET compared to those after 2 cycles of STANFORD V chemotherapy in HOD08 and HOD05, respectively.
  • Event-free survival [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment ]
    Time to event defined as relapse, progression or death. The EFS for the high-risk patients is compared to those in HLHR13.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17
Official Title  ICMJE Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17
Brief Summary This is a phase II study using risk and response-adapted therapy for low, intermediate and high risk classical Hodgkin lymphoma. Chemotherapy regimens will be based on risk group assignment. Low-risk and intermediate- risk patients will be treated with bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine, and prednisone (BEABOVP) chemotherapy. High-risk patients will receive Adcetris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) (AEPA) and cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC) (CAPDac) chemotherapy. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an adequate response (AR) after 2 cycles of therapy for all risk groups.
Detailed Description

PRIMARY OBJECTIVES

  • To evaluate the efficacy (adequate response) after 2 cycles of BEABOVP (bendamustine substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in low-risk and intermediate-risk patients with classical Hodgkin lymphoma (cHL).
  • To estimate the event-free survival in high-risk patients with classical Hodgkin lymphoma (cHL).

SECONDARY OBJECTIVES

  • To describe the acute hematologic and infectious toxicities of BEABOVP (bendamustine substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in patients with low-risk and intermediate- risk cHL as they relate to transfusion requirements, hematopoietic growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
  • To describe the acute hematologic, neuropathic, and infectious toxicities of AEPA/CAPDac in patients with high-risk cHL as they relate to transfusion requirements, hematopoietic growth factor support, episodes of grade 3 and 4 sensory or motor neuropathy, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
  • To evaluate patterns of failure in irradiated and non-irradiated patients.
  • To estimate the EFS functions of LR and IR patients, and compare with those in previously published studies.
  • To estimate the response rate in HR patients and compare with historical and literature rates.
  • To compare response rates in LR and IR patients with historical and literature rates.
  • To compare the EFS function of HR patients with that in previously published studies.

EXPLORATORY OBJECTIVES

  • To evaluate the plasma pharmacokinetics of bendamustine along with predictors of its variability when used as part of BEABOVP regimen for pediatric cHL patients.
  • To explore the patterns and dynamics of T-cell clonality in classical Hodgkin lymphoma.
  • To explore the association between TARC, total metabolic tumor volume, stage, risk group and treatment response.
  • To obtain baseline testing by St. Jude Lifetime Study (SJLIFE) to allow for enhanced survivorship follow-up

Low-risk and Intermediate-risk: Low-risk patients will receive 2 cycles of BEABOVP and Intermediate-risk patients will receive 3 cycles of BEABOVP.

BEABOVP regimen: Patients will receive bendamustine day 1, etoposide day 15, Adriamycin® (doxorubicin) days 1 and 15, bleomycin days 8 and 22, Oncovin® (vincristine) days 8 and 22, vinblastine days 1 and 15, and prednisone two or three times daily every other day for 14 days of each cycle.

High-risk patients will receive 2 cycles of AEPA and 4 cycles of CAPDac.

AEPA regimen: Patients will receive Adcedris® (brentuximab vedotin) days 1, 8 and 15, etoposide days 1 to 5, prednisone two or three times daily days 1 to 15 and Adriamycin® (doxorubicin) days 1 and 15.

CAPDac regimen: Patients will receive cyclophosphamide days 1 and 8, Adcetris® (brentuximab vedotin) days 1 and 8, prednisone two or three times daily days 1 to 15 and Dacarbazine® (DTIC) days 1 to 3.

Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy for all risk groups.

Steroids will be omitted after 2 cycles for any IR or HR patient with an AR after 2 cycles of therapy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: bendamustine
    Given intravenously (IV)
    Other Name: TREANDA (R)
  • Drug: Etoposide
    Given intravenously (IV)
    Other Names:
    • VP-16
    • Vepeside
  • Drug: Doxorubicin
    Given intravenously (IV)
    Other Name: Adriamycin (R)
  • Drug: Bleomycin
    Given intravenously (IV)
    Other Name: Blenoxane (R)
  • Drug: Vincristine
    Given intravenously (IV)
    Other Name: Oncovin (R)
  • Drug: Vinblastine
    Given intravenously (IV)
    Other Name: Velban (R)
  • Drug: Prednisone
    Given orally (PO)
    Other Name: Prednisolone
  • Drug: Filgrastim
    Given subcutaneously (SQ) or IV
    Other Name: Neupogen (R)
  • Drug: Brentuximab Vedotin
    Given intravenously (IV)
    Other Name: Adcetris
  • Drug: Cyclophosphamide
    Given intravenously (IV)
    Other Name: Cytoxan (R)
  • Drug: DTIC
    Given intravenously (IV)
    Other Names:
    • DACARBAZINE (R)
    • Dimethyl Triazeno Imidazole Carboximide
  • Other: Quality of Life Measurements
    Quality of Life measurements will be done in low-risk cycles 1 and 2 BEABOVP, intermediate-risk cycles 1, 2 and 3 BEABOVP and high-risk cycles 1 and 2 AEPA and cycles 1, 2, 3, and 4 CAPDac. QOL will be done at year 1, 2 and 5 for all risk groups.
    Other Name: Quality of Life Measurements (QOL)
  • Radiation: Radiotherapy
    Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy for all risk groups. Radiotherapy will be administered after completion of all chemotherapy upon hematologic count recovery.
    Other Names:
    • radiation therapy
    • irradiation
Study Arms  ICMJE
  • Experimental: Low-Risk
    Participants receive 2 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. Filgrastim may be given as clinically indicated. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements will be done.
    Interventions:
    • Drug: bendamustine
    • Drug: Etoposide
    • Drug: Doxorubicin
    • Drug: Bleomycin
    • Drug: Vincristine
    • Drug: Vinblastine
    • Drug: Prednisone
    • Drug: Filgrastim
    • Other: Quality of Life Measurements
    • Radiation: Radiotherapy
  • Experimental: Intermediate-Risk
    Participants receive 3 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements will be done.
    Interventions:
    • Drug: bendamustine
    • Drug: Etoposide
    • Drug: Doxorubicin
    • Drug: Bleomycin
    • Drug: Vincristine
    • Drug: Vinblastine
    • Drug: Prednisone
    • Drug: Filgrastim
    • Other: Quality of Life Measurements
    • Radiation: Radiotherapy
  • Experimental: High-Risk
    Participants receive 2 cycles of AEPA: Adcedris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) and 4 cycles of CAPDac: cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC). For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements will be done.
    Interventions:
    • Drug: Etoposide
    • Drug: Doxorubicin
    • Drug: Prednisone
    • Drug: Filgrastim
    • Drug: Brentuximab Vedotin
    • Drug: Cyclophosphamide
    • Drug: DTIC
    • Other: Quality of Life Measurements
    • Radiation: Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2018)
200
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2018)
125
Estimated Study Completion Date  ICMJE July 1, 2028
Estimated Primary Completion Date January 1, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed, previously untreated CD30+ classical HL. (Participants are still eligible if they received limited emergent RT or steroid therapy - maximum of 7 days if within the last month or as approved by PI).
  • Age ≤ 21 years at the time of diagnosis (i.e., participants are eligible until their 22nd birthday) for low-risk and intermediate-risk
  • Age ≤ 18 years at the time of diagnosis (i.e., participants are eligible until their 19th birthday) for high-risk
  • All Ann Arbor stages.

    • Low-Risk: IA, IIA (excluding patients with "E" lesions or mediastinal bulk)
    • Intermediate-Risk: IA or IIA with "E" lesions or bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph) and IB, IIIA.
    • High-Risk: IIB, IIIB, IV
  • Adequate renal function based on GFR ≥ 70 ml/min/1.73m2 OR serum creatinine adjusted for age and gender as follows: Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for males and 0.6 mg/dL for females, Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for males and 0.8 mg/dL for females, Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for males and 1 mg/dL for females, Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for males and 1.2 mg/dL for females, Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females, Age ≥16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females
  • Adequate hepatic function (total bilirubin ≤ 1.5 x ULN for age, and AST/ALT ≤ 2.5 x ULN for age).
  • Adequate hematologic criteria at baseline, unless secondary to Hodgkin disease diagnosis

    • Absolute neutrophil count (ANC) ≥1000/µL
    • Platelets ≥ 75,000/µL
  • Adequate cardiac function defined as shortening fraction of ≥ 27% by echocardiogram or MUGA, unless decreased function is due to large mediastinal mass or effusion related to HL.
  • Adequate pulmonary function defined as no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 92% on room air unless secondary to a large mediastinal mass or effusion related to HL.
  • Female participant who is post-menarchal must have a negative urine or serum pregnancy test.
  • Female or male participant of reproductive potential must agree to use an effective contraceptive method throughout duration of study treatment.

Exclusion Criteria:

  • CD30 negative HL.
  • Has received prior therapy for Hodgkin lymphoma
  • Inadequate organ function
  • High-risk participants with a history of ≥ grade 2 peripheral neuropathy or any active neurologic disease, that in the opinion of the treating investigator, would impede ability to assess neurologic toxicities.
  • Inability or unwillingness of research participant or legal guardian / representative to give written informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jamie Flerlage, MD, MS 866-278-5833 referralinfo@stjude.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03755804
Other Study ID Numbers  ICMJE cHOD17
NCI-2018-02924 ( Registry Identifier: NCI Clinical Trial Registration Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party St. Jude Children's Research Hospital
Study Sponsor  ICMJE St. Jude Children's Research Hospital
Collaborators  ICMJE
  • Teva Pharmaceuticals USA
  • Seattle Genetics, Inc.
Investigators  ICMJE
Principal Investigator: Jamie Flerlage, MD, MS St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP