Clinical Trial: NCT03755804 - My Cancer Genome

NCT03755804

Description:

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.

Related Conditions:

Classical Hodgkin Lymphoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03755804

Trial Eligibility

Document

Title

Brief Title: Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17
Official Title: Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17

Clinical Trial IDs

ORG STUDY ID: cHOD17
SECONDARY ID: NCI-2018-02924
NCT ID: NCT03755804

Conditions

Hodgkin Lymphoma

Interventions

Drug	Synonyms	Arms
bendamustine	TREANDA (R)	Intermediate-Risk
Etoposide	VP-16, Vepeside	High-Risk
Doxorubicin	Adriamycin (R)	High-Risk
Bleomycin	Blenoxane (R)	Intermediate-Risk
Vincristine	Oncovin (R)	Intermediate-Risk
Vinblastine	Velban (R)	Intermediate-Risk
Prednisone	Prednisolone	High-Risk
Filgrastim	Neupogen (R)	High-Risk
Brentuximab Vedotin	Adcetris	High-Risk
Cyclophosphamide	Cytoxan (R)	High-Risk
DTIC	DACARBAZINE (R), Dimethyl Triazeno Imidazole Carboximide	High-Risk

Purpose

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 establish next generation sequencing of ctDNA as a reliable method of non-invasively
           profiling tumor-associated mutations in pediatric patients with HL.

        -  To determine if kinetics of ctDNA in patients with pediatric HL during treatment are
           predictive of outcome.

        -  To obtain baseline testing by St. Jude Lifetime Study (SJLIFE) to allow for enhanced
           survivorship follow-up:

             -  Neurologic testing

             -  Neurocognitive testing

             -  Quantitative brain imaging

             -  Polysomnography

             -  Cardiovascular testing (valvular testing, arterial elasticity, carotid-femoral
                pulse wave velocity, orthostatic hypotension, heart rate variability

             -  Neuropathy screening

             -  Changes in body mass index composition during therapy

      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 per day every other day of each
      cycle for a total of 14 days of steroids.

      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.

Trial Arms

Name	Type	Description	Interventions
Low-Risk	Experimental	Participants receive 2 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. 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.	bendamustine Etoposide Doxorubicin Bleomycin Vincristine Vinblastine Prednisone Filgrastim
Intermediate-Risk	Experimental	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. Dexrazoxane may be given at the discretion of the treating investigator. 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.	bendamustine Etoposide Doxorubicin Bleomycin Vincristine Vinblastine Prednisone Filgrastim
High-Risk	Experimental	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. Dexrazoxane may be given at the discretion of the treating investigator. 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.	Etoposide Doxorubicin Prednisone Filgrastim Brentuximab Vedotin Cyclophosphamide DTIC

Eligibility Criteria

        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 ≤ 25 years at the time of diagnosis (i.e., participants are eligible until their
             26th 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 would impede the ability to assess neurologic toxicities.

          -  Inability or unwillingness of research participant or legal guardian / representative
             to give written informed consent.

Maximum Eligible Age:	25 Years
Minimum Eligible Age:	N/A
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Response rate of adequate response
Time Frame:	after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment
Safety Issue:
Description:	The 70 evaluable low-risk patients enrolled will be evaluated for this objective.

Secondary Outcome Measures

Measure:	Number of adverse events in low-risk and intermediate-risk patients
Time Frame:	From enrollment to end of therapy (approximately 8 months
Safety Issue:
Description:	According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

Measure:	Number of adverse events in high-risk patients
Time Frame:	From enrollment to end of therapy (approximately 8 months
Safety Issue:
Description:	According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

Measure:	Local failure rate
Time Frame:	From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment
Safety Issue:
Description:	Local failure rate in irradiated and non-irradiated patients

Measure:	Event-free survival
Time Frame:	From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment
Safety Issue:
Description:	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.

Measure:	Response rate
Time Frame:	after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment
Safety Issue:
Description:	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.

Measure:	Response rate
Time Frame:	after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment
Safety Issue:
Description:	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.

Measure:	Event-free survival
Time Frame:	From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment
Safety Issue:
Description:	Time to event defined as relapse, progression or death. The EFS for the high-risk patients is compared to those in HLHR13.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	St. Jude Children's Research Hospital

Trial Keywords

Hodgkin Lymphoma
Pediatric Cancer
Frontline Therapy
Response Adapted Therapy
Risk Adapted Therapy

Last Updated

March 15, 2021

Clinical Trials /

Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17