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Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05389423
Recruitment Status : Not yet recruiting
First Posted : May 25, 2022
Last Update Posted : August 5, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Non-Hodgkin lymphoma (NHL) is the most common cancer among people living with HIV in the United States. People with HIV are up to 17 times more likely to get NHL than people who do not have HIV. The disease may also be different in these two groups. More study is needed for treating

people with both HIV and NHL.

Objective:

To test a study drug (pomalidomide) in combination with chemotherapy with or without another drug (rituximab) in people with HIV-associated NHL.

Eligibility:

Adults aged 18 years or older diagnosed with HIV-associated B-cell NHL with high-risk features.

Design:

Participants will undergo screening. They will have a physical exam. They will have blood and urine tests and tests of heart function. They may have imaging scans. Researchers will review tissue samples of participant s tumors. In some cases, a new biopsy may be needed.

Participants will receive up to 6 cycles of treatment.

The first cycle is 26 days: Participants will take pomalidomide by mouth for 10 days. After 5 days they will start receiving chemotherapy drugs through a tube attached to a needle placed in a vein (IV). Some participants will receive rituximab on day 5. All participants will receive a second set of IV drugs that will last for 4 days (96 hours). They will receive another IV drug after the previous treatment is complete.

The remaining cycles are each 21 days. Participants will take pomalidomide by mouth for the first 10 days. Other chemotherapy treatments will also be repeated starting on day 1 of each cycle.

Screening tests will be repeated at study visits.

Follow-up visits will continue for 4 years.


Condition or disease Intervention/treatment Phase
Diffuse Large Cell Lymphoma Non-Hodgkin Lymphoma Burkitt Lymphoma Plasmablastic Lymphoma B-Cell Neoplasm Drug: Vincristine Drug: Prednisone Drug: Doxorubicin Drug: Etoposide Drug: Pomalidomide Drug: Cyclophosphamide Drug: Rituximab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas
Estimated Study Start Date : August 10, 2022
Estimated Primary Completion Date : June 1, 2028
Estimated Study Completion Date : June 1, 2032


Arm Intervention/treatment
Experimental: 1/Dose Escalation
Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin
Drug: Vincristine
0.4 mg/m2/day administered by CIVI on days 1 to 4

Drug: Prednisone
60 mg/m2/day administered orally on days 1 to 5

Drug: Doxorubicin
10 mg/m2/day administered by CIVI on days 1 to 4

Drug: Etoposide
50 mg/m2/day administered by CIVI on days 1 to 4

Drug: Pomalidomide
An initial dose of 3mg administered orally for 10 days in all cycles. In cycle 1, it will start 5 days before DA-EPOCH; in cycles 2-6, it will start on day 1. Administered at an MTD dose for the expansion phase.

Drug: Cyclophosphamide
750 mg/m2 administered IV on day 5

Drug: Rituximab
375 mg/m2 administered IV on day 1 (only for CD20+ tumors)

Experimental: 2/Dose Expansion
Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and
Drug: Vincristine
0.4 mg/m2/day administered by CIVI on days 1 to 4

Drug: Prednisone
60 mg/m2/day administered orally on days 1 to 5

Drug: Doxorubicin
10 mg/m2/day administered by CIVI on days 1 to 4

Drug: Etoposide
50 mg/m2/day administered by CIVI on days 1 to 4

Drug: Pomalidomide
An initial dose of 3mg administered orally for 10 days in all cycles. In cycle 1, it will start 5 days before DA-EPOCH; in cycles 2-6, it will start on day 1. Administered at an MTD dose for the expansion phase.

Drug: Cyclophosphamide
750 mg/m2 administered IV on day 5

Drug: Rituximab
375 mg/m2 administered IV on day 1 (only for CD20+ tumors)




Primary Outcome Measures :
  1. safety and tolerability [ Time Frame: 6 cycles of treatment, or until confirmed progression, unacceptable toxicity or trial withdrawal ]
    The fraction of patients with toxicity noted at each dose level will be reported by grade and type of toxicity identified. Maximum tolerated dose will also be reported.


Secondary Outcome Measures :
  1. progression-free survival [ Time Frame: every 3 weeks for the first 6 cycles, every 3 months for the rest of the first year, then every 6 months for 4 years (5 years total). ]
    duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first

  2. preliminary estimates of response [ Time Frame: every 3 weeks for the first 6 cycles, every 3 months for the rest of the first year, then every 6 months for 4 years (5 years total). ]
    Percentage of participants with the best overall response of CR or PR to therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Participants must have histologically or cytologically confirmed B-cell non-Hodgkin lymphoma confirmed by the Laboratory of Pathology, NCI, with one or more of the following features:

    • Leptomeningeal/CSF involvement
    • High-risk for CNS relapse per CNS-IPI (score 4-6)
    • Plasmablastic histology
    • Gammaherpesvirus positive tumor
    • Presence of Kaposi sarcoma
  • Measurable or evaluable lymphoma.
  • Positive HIV1/2 serology.
  • Participants may not have received prior curative-intent chemotherapy for lymphoma.
  • Participants who have received prior treatment as a bridge to curative-intent therapy will be considered per Protocol Chair discretion if >= 2 weeks since administration.
  • Age >=18 years
  • ECOG performance status <=4
  • Persons of childbearing potential (PCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior to and again within 1 day before starting pomalidomide and must either commit to continued abstinence from penetrative vaginal intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before the participant starts taking pomalidomide and for 28 days after the last dose of pomalidomide.
  • All study participants must agree to be registered into the mandatory POMALYST REMS[Registered]TM program and be willing and able to comply with the requirements of the POMALYST REMS[Registered]TM program.
  • Able to take aspirin 81mg orally daily or another substitute thromboprophylaxis.
  • Participants must have adequate organ and marrow function as defined below unless abnormalities are attributed to lymphoma or HIV as determined by investigator:

    • absolute neutrophil count >=1,000/mcL
    • platelets >=75,000/mcL
    • total bilirubin <=1.5 X institutional upper limit of normal (participants with history of Gilbert disease are eligible if total bilirubin <= 5 mg/dL with <80% unconjugated bilirubin)
    • AST(SGOT)/ALT(SGPT) <=3 X institutional upper limit of normal
    • creatinine clearance >=60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal.
  • Participants with hepatitis B virus (HBV) infection must be on suppressive antiviral therapy.
  • Participants must be willing to take and adhere to antiretroviral therapy (participants are not required to be on any specific regimen of antiretroviral therapy).
  • Participants must understand and sign a written informed consent document.

EXCLUSION CRITERIA:

  • Participants who are receiving any other investigational agents.
  • Participants requiring any of the agents listed as prohibited thearapies.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide or other agents used in study.
  • Parenchymal brain involvement with lymphoma.
  • Ejection fraction less than 40% by echocardiography (ECHO)
  • CTCAEv5.0 Grade 3-4 neuropathy
  • History of malignant tumors other than Kaposi sarcoma or KSHV-associated multicentric Castleman Disease, unless:

    • In complete remission for >= 1 year from the time response was first documented; or,
    • Completely resected basal cell carcinoma; or,
    • In situ squamous cell carcinoma of the cervix or anus; or,
    • Prior or concurrent malignancy has a natural history or treatment which does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen per Protocol Chair discretion.
  • Known drug-related, inherited, or acquired procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome.
  • Symptomatic congestive heart failure
  • Unstable angina pectoris, or cardiac arrhythmia.
  • Uncontrolled intercurrent illness or participants considered to be of poor medical health due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active uncontrolled infection (excluding lymphoma or HIV) as documented in prior records or suggested by medical history, physical examination or standard clinical assessments such as imaging and laboratory studies.
  • Pregnant or breast-feeding persons (if lactating, must agree not to breast feed while taking pomalidomide).

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): NCT05389423


Contacts
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Contact: Anaida Widell (240) 760-6074 anaida.widell@nih.gov
Contact: Kathryn A Lurain, M.D. (301) 250-5156 kathryn.lurain@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Kathryn A Lurain, M.D. National Cancer Institute (NCI)
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05389423    
Other Study ID Numbers: 10000274
000274-C
First Posted: May 25, 2022    Key Record Dates
Last Update Posted: August 5, 2022
Last Verified: July 19, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: . All IPD recorded in the medical record will be shared with intramural investigators upon request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Non-Hodgkin Lymphoma
Epstein Barr Virus
Plasmablastic Lymphoma
Chemotherapy
Immune Modulatory
Additional relevant MeSH terms:
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Burkitt Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Plasmablastic Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, AIDS-Related
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Infections
Tumor Virus Infections
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Vincristine
Pomalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs