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

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ClinicalTrials.gov Identifier: NCT03527628
Recruitment Status : Recruiting
First Posted : May 17, 2018
Last Update Posted : May 17, 2018
Sponsor:
Information provided by (Responsible Party):
King Abdullah International Medical Research Center

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.

Condition or disease Intervention/treatment Phase
Classical Hodgkin Lymphoma Hodgkin Lymphoma (Category) Hodgkin Disease Hodgkin Lymphoma Drug: Adriamycin Drug: Cyclophosphamide Drug: Vinblastine Drug: Dacarbazine Drug: Brentuximab Vedotin Drug: ABVD Phase 2

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With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative.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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : January 15, 2021
Estimated Study Completion Date : January 15, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Patients with PET-2 Negative Result

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)

Drug: Adriamycin
25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.
Other Name: Doxorubicin

Drug: Cyclophosphamide
400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle
Other Names:
  • Cytoxan®
  • Neosar®
  • Cycloblastin
  • Revimmune

Drug: Vinblastine
6mg/m2 Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, in days 1 and 15 of each 28 day cycle
Other Name: Velbe ®

Drug: Dacarbazine
375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle
Other Name: DTIC

Drug: ABVD
All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2)
Other Name: (Adriamycin, Bleomycin, Vinblastine and Dacarbazine )

Patients with PET-2 Positive Result

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

Drug: Adriamycin
25mg/m2 Bolus injection via fast running drip of 0.9% NaCl in days 1 and 15 of each 28 day cycle.
Other Name: Doxorubicin

Drug: Cyclophosphamide
400mg/m2 Infusion in 500ml sodium chloride 0.9%over 30min. in days 1 and 15 of each 28 day cycle
Other Names:
  • Cytoxan®
  • Neosar®
  • Cycloblastin
  • Revimmune

Drug: Vinblastine
6mg/m2 Intravenous infusion in 50ml sodium chloride 0.9% over 10 minutes, in days 1 and 15 of each 28 day cycle
Other Name: Velbe ®

Drug: Dacarbazine
375mg/m2 Infusion in 500mls 0.9% NaCI over least 60mins. in days 1 and 15 of each 28 day cycle
Other Name: DTIC

Drug: Brentuximab Vedotin
1.2mg/kg Intravenous infusion, in days 1 and 15 of each 28 day cycle
Other Names:
  • ADCETRIS®
  • SGN-35

Drug: ABVD
All enrolled patients receive 2 cycles of ABVD (Adriamycin 25mg/m2, Bleomycin10,000units/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2)
Other Name: (Adriamycin, Bleomycin, Vinblastine and Dacarbazine )




Primary Outcome Measures :
  1. ]Progression Free Survival (PFS) [ Time Frame: 3 years ]

    3 year 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 :
  1. Overall Survival (OS) [ Time Frame: From the date of diagnosis up to study completion or death, whichever came first, assessed up to 5 years ]
    Superior overall survival of PET 2 positive patients treate with ACVD + BV after 2 cycles of ABVD and PET 2 negative treated with ACVD after 2 cycles of ABVD


Other Outcome Measures:
  1. Reduction of lung toxicity [ Time Frame: 6 months ]
    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

  2. Overall toxicity [ Time Frame: 6 months ]
    The feasibility of the entire program in terms of grade 3 or 4 NCICTCAE or WHO toxicity



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Ages Eligible for Study:   14 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

      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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03527628


Contacts
Contact: Ayman Alhejazi, MD 801 1111 ext 53388 hejazia@ngha.med.sa

Locations
Saudi Arabia
King Abdulaziz Medical City, Ministry of National Guard Recruiting
Riyadh, Saudi Arabia, 22390
Contact: Ayman Hejazi, MD    +966 8011111 ext 53388    hejazia@ngha.med.sa   
Sponsors and Collaborators
King Abdullah International Medical Research Center
Investigators
Principal Investigator: Ayman Hejazi, MD King Abdulaziz Medical City, Ministry of National Gaurd (KAMC)

Responsible Party: King Abdullah International Medical Research Center
ClinicalTrials.gov Identifier: NCT03527628     History of Changes
Other Study ID Numbers: RC-16/150
First Posted: May 17, 2018    Key Record Dates
Last Update Posted: May 17, 2018
Last Verified: October 2017

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

Keywords provided by King Abdullah International Medical Research Center:
Stage II B Classical Hodgkin Lymphoma
Stage III Classical Hodgkin Lymphoma
Stage IV Classical Hodgkin Lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Liposomal doxorubicin
Doxorubicin
Bleomycin
Vinblastine
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents