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OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy ((Optimist))

Primary Purpose

Classical Hodgkin Lymphoma, Hodgkin Lymphoma (Category), Hodgkin Disease

Status
Unknown status
Phase
Phase 2
Locations
Saudi Arabia
Study Type
Interventional
Intervention
Adriamycin
Cyclophosphamide
Vinblastine
Dacarbazine
Brentuximab Vedotin
ABVD
Sponsored by
King Abdullah International Medical Research Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Classical Hodgkin Lymphoma focused on measuring Stage II B Classical Hodgkin Lymphoma, Stage III Classical Hodgkin Lymphoma, Stage IV Classical Hodgkin Lymphoma

Eligibility Criteria

14 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • All the following parameters should be met

    • Newly diagnosed untreated ,histologically proven CD30 positive classical Hodgkin Lymphoma (cHL)
    • Advanced stage (Stage IIB to IVB) as defined by Ann Arbor Staging System (Appendix 1)
    • Age ≥ 14, < 60 years
    • ECOG performance status 0-2
    • Written informed consent for the trial
    • Adequate contraceptive precautions for all patients of childbearing potential
    • All prognostic group

Exclusion Criteria:

  • Any of the following:

    • Pregnant or lactating women.

    • Presence of the following:

      1. Heart failure with LVEF <50%
      2. Liver enzymes, >2 ULN not attributed to Hodgkin Lymphoma.
      3. Another malignancy that is currently clinically significant or requires active intervention
    • Early-stage disease (Stage I- IIA).
    • Patients who are already participating to another clinical trial.
    • Known history of HIV seropositive status
    • ECOG performance status 3-4
    • Creatinin clearance <50 ml/min
    • Prior treatment for Hodgkin Lymphoma excluding steroids
    • Medical or psychiatric conditions compromising the patient's ability to give informed consent
    • Patients with serious active infection
    • Pre-existing peripheral neuropathy (grade 2 or more).

Sites / Locations

  • King Abdulaziz Medical City, Ministry of National GuardRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Patients with PET-2 Negative Result

Patients with PET-2 Positive Result

Arm Description

After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)

After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin

Outcomes

Primary Outcome Measures

]Progression Free Survival (PFS)
PFS is estimated from the date of diagnosis until the date of first disease progression or relapse, death for any cause. Superior overall 3 year progression-free survival of patients with PET 2 positive after 2 cycles of ABVD with ACVD and BV compared to historical control of ABVD treated patients and PET 2 negative patients with ACVD only after 2 cycles of ABVD.

Secondary Outcome Measures

Overall Survival (OS)
Superior overall survival of PET 2 positive patients treated with ACVD + BV after 2 cycles of ABVD and PET 2 negative treated with ACVD after 2 cycles of ABVD. It is estimated from the date of diagnosis up to study completion or death, whichever came first, assessed up to 5 years.

Full Information

First Posted
December 12, 2017
Last Updated
November 14, 2019
Sponsor
King Abdullah International Medical Research Center
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1. Study Identification

Unique Protocol Identification Number
NCT03527628
Brief Title
OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy
Acronym
(Optimist)
Official Title
A Phase II, Multicenter, Open Label Study of Treatment Intensification With ACVD and Brentuximab-Vedotin in Advanced-stage Hodgkin Lymphoma Patients With a Positive Interim PET Scan After 2 ABVD Cycles
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
January 15, 2021 (Anticipated)
Study Completion Date
January 15, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
King Abdullah International Medical Research Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a prospective, multi-center, open-label, phase II clinical trial, aims to assess the effectiveness of the combination ACVD (Adriamycin, Cyclophosphamide, Vinblastine and Dacarbazine) and BV (Brentuximab Vedotin) in PET-2 positive advanced-stage HL patients, in order to improve the overall long-term disease control in the entire cohort of advanced-stage HL.
Detailed Description
With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative. All advanced stage HL patients will receive 2 cycles of the standard treatment ABVD and assessed with PET-2 scan. Knowing that Cyclophosphamide toxicities include cytopenias, amenorrhea and male infertility. These toxicities are mainly dependent on the total cumulative dose. Doses less than 4 g/m2 are not associated with sterility or major toxicity, doses higher than this can lead to azoospermia which was reversible in many cases therefore the cumulative dose will be used in this study is 3200 mg. Additionally, Brentuximab Vedotin has shown significant activity in relapsed refractory HL with minor toxicities. PET scan after 2 cycles of ABVD has proven to be an excellent tool to identify patients that will have long term PFS of 95% when it is negative and only progression-free survival (PFS) of less than 15% when it is positive. The primary endpoint of the study will be to assess the overall 3-Y PFS of the entire cohort of patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Classical Hodgkin Lymphoma, Hodgkin Lymphoma (Category), Hodgkin Disease, Hodgkin Lymphoma
Keywords
Stage II B Classical Hodgkin Lymphoma, Stage III Classical Hodgkin Lymphoma, Stage IV Classical Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients with PET-2 Negative Result
Arm Type
Other
Arm Description
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)
Arm Title
Patients with PET-2 Positive Result
Arm Type
Other
Arm Description
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin
Intervention Type
Drug
Intervention Name(s)
Adriamycin
Other Intervention Name(s)
Doxorubicin
Intervention Description
25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan®, Neosar®, Cycloblastin, Revimmune
Intervention Description
400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle
Intervention Type
Drug
Intervention Name(s)
Vinblastine
Other Intervention Name(s)
Velbe ®
Intervention Description
6mg/m2 Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, in days 1 and 15 of each 28 day cycle
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Other Intervention Name(s)
DTIC
Intervention Description
375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle
Intervention Type
Drug
Intervention Name(s)
Brentuximab Vedotin
Other Intervention Name(s)
ADCETRIS®, SGN-35
Intervention Description
1.2mg/kg Intravenous infusion, in days 1 and 15 of each 28 day cycle
Intervention Type
Drug
Intervention Name(s)
ABVD
Other Intervention Name(s)
(Adriamycin, Bleomycin, Vinblastine and Dacarbazine )
Intervention Description
All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2)
Primary Outcome Measure Information:
Title
]Progression Free Survival (PFS)
Description
PFS is estimated from the date of diagnosis until the date of first disease progression or relapse, death for any cause. Superior overall 3 year progression-free survival of patients with PET 2 positive after 2 cycles of ABVD with ACVD and BV compared to historical control of ABVD treated patients and PET 2 negative patients with ACVD only after 2 cycles of ABVD.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Superior overall survival of PET 2 positive patients treated with ACVD + BV after 2 cycles of ABVD and PET 2 negative treated with ACVD after 2 cycles of ABVD. It is estimated from the date of diagnosis up to study completion or death, whichever came first, assessed up to 5 years.
Time Frame
5 years
Other Pre-specified Outcome Measures:
Title
Reduction of lung toxicity
Description
The ability of ACVD to reduce lung toxicity as compared to ABVD by performing a pulmonary function test (PFT) at baseline and end of treatment
Time Frame
6 months
Title
Overall toxicity
Description
The feasibility of the entire program in terms of grade 3 or 4 NCICTCAE or WHO toxicity
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All the following parameters should be met Newly diagnosed untreated ,histologically proven CD30 positive classical Hodgkin Lymphoma (cHL) Advanced stage (Stage IIB to IVB) as defined by Ann Arbor Staging System (Appendix 1) Age ≥ 14, < 60 years ECOG performance status 0-2 Written informed consent for the trial Adequate contraceptive precautions for all patients of childbearing potential All prognostic group Exclusion Criteria: Any of the following: Pregnant or lactating women. Presence of the following: Heart failure with LVEF <50% Liver enzymes, >2 ULN not attributed to Hodgkin Lymphoma. Another malignancy that is currently clinically significant or requires active intervention Early-stage disease (Stage I- IIA). Patients who are already participating to another clinical trial. Known history of HIV seropositive status ECOG performance status 3-4 Creatinin clearance <50 ml/min Prior treatment for Hodgkin Lymphoma excluding steroids Medical or psychiatric conditions compromising the patient's ability to give informed consent Patients with serious active infection Pre-existing peripheral neuropathy (grade 2 or more).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ayman Alhejazi, MD
Phone
801 1111
Ext
53388
Email
hejazia@ngha.med.sa
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayman Hejazi, MD
Organizational Affiliation
King Abdulaziz Medical City, Ministry of National Gaurd (KAMC)
Official's Role
Principal Investigator
Facility Information:
Facility Name
King Abdulaziz Medical City, Ministry of National Guard
City
Riyadh
ZIP/Postal Code
22390
Country
Saudi Arabia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ayman Hejazi, MD
Phone
+966 8011111
Ext
53388
Email
hejazia@ngha.med.sa

12. IPD Sharing Statement

Learn more about this trial

OPTmizing Advanced Stage HodgkIn LymphoMa patIentS Therapy

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