Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas

NCT02228512 | Withdrawn Phase 1

• 2 other identifiers: 14017614-C-0176
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: \- The chemotherapy combination DA-EPOCH-RP includes the drugs etoposide (E), prednisone (P), vincristine (O), cyclophosphamide (C), doxorubicin (H), rituximab (R), and pomalidomide (P). Researchers want to see if including pomalidomide will help people with two rare lymphomas. Objectives: \- To study the safety and efficacy of the chemotherapy drugs DA-EPOCH-RP. Eligibility: \- Adults at least 18 years old. They must have primary effusion lymphoma or large cell lymphoma arising from Kaposi sarcoma Herpesvirus-associated multicentric Castleman disease. Design:

• Participants will be with screened with blood tests, scans, spinal tap, and bone marrow sample. They may have skin or lymph node samples taken and fluid removed from around some organs.
• Participants will have breathing and eye tests. A camera may take pictures inside their body.
• Participants will take pomalidomide alone by mouth for up to 21 days. Then they will get rituximab by intravenous (IV) catheter, which is a small tube that goes into a vein..
• Participants will have an IV inserted in an arm or chest vein to get the IV chemotherapy drugs, at the same time the will take pomalidomide by mouth for 5 days.
• They will get DA-EPOCH-RP in 21-day cycles. Most people will have 6 cycles.
• They will get 4 study drugs by IV for 5 days and 2 others by mouth for 5 days.
• They will get daily filgrastim injections in the skin until white blood counts are acceptable
• For 2 days of some cycles, methotrexate will be injected into the spinal fluid.
• After completing EPOCH-RP, some participants who have Kaposi sarcoma will be prescribed pomalidomide for 3-weeks, followed by a one week break, for up to 12 months.
• Participants will repeat the blood tests often. They will also have repeated medical history, physical exam, urine and stool tests, and pictures of any rashes associated with these lymphomas.
• Participants will have several follow-up visits over 4 years.

Conditions

Large Cell Lymphoma Arising in KSHV-associated Multicentric Castleman Disease; Primary Effusion Lymphoma

Keywords

HHV8; PEL; Immune Modulation; CC-4047; IMiD

Outcome Measures

Primary Outcomes (1)

• (Phase I) To determine the maximum tolerated dose and/or recommended phase II dose of pomalidomide in combination with DA-EPOCH-R.

  one-year

Secondary Outcomes (2)

• (Phase II) Evaluate overall survival in treatment naive patients with primary effusion lymphoma treated with pomalidomide in combination with modified DA-EPOCH-RP

  one-year

• Evaluate response rates and progression free survival

  one-year

Study Arms (3)

1

ACTIVE COMPARATOR

Treatment naive PEL (main cohort)

Drug: Pomalidomide; Drug: Rituximab; Drug: Prednisone; Drug: Etoposide; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide

2

ACTIVE COMPARATOR

Treatment na(SqrRoot) ve large cell lymphoma arising in KSHV-MCD

Drug: Pomalidomide; Drug: Rituximab; Drug: Prednisone; Drug: Etoposide; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide

3

ACTIVE COMPARATOR

Previously treated KSHV-NHL

Drug: Pomalidomide; Drug: Rituximab; Drug: Prednisone; Drug: Etoposide; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide

Interventions

Pomalidomide DRUG

Part A: 5 mg po daily for 21 days (full course) Part A: 5 mg po daily for 4 days (short course) Part B: 5 mg po daily for 5 days (Phase I/II dose) Part C: Phase I/II dose) po daily Day 1-21 of 28 day cycle for up to 12 cycles.

1; 2; 3

Rituximab DRUG

Part A: 375 mg/m2 day 22 (full course) Part A: 375 mg/m2 day 5 (short course) Part A: 375 mg/m2 day 1 (omit pomalidomode) Part B: 375 mg/m2 day 1

1; 2; 3

Prednisone DRUG

Part B: 60 mg/m2/day po x 5 days (day 1-5

1; 2; 3

Etoposide DRUG

Part B: 50 mg/m2/day CIVI over 24 hrs x 4 days

1; 2; 3

Doxorubicin DRUG

Part B: 10 mg/m2/day CIVI over 24 hrs x 4 days

1; 2; 3

Vincristine DRUG

Part B: 0.4 mg/m2/day CIVI over 24 hrs x 4 days

1; 2; 3

Cyclophosphamide DRUG

Part B: 750 mg/m2 Day 5

1; 2; 3

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• KSHV-associated non-Hodgkin lymphoma, with pathology reviewed and confirmed at the NIH. May include WHO recognized tumors
• Primary effusion lymphoma (PEL), including extracavitary variant
• Large cell lymphoma arising in the setting of KSHV-associated MCD.
• Measurable or assessable lymphoma
• Any HIV status
• Age 18 years or greater. Because no dosing or adverse event data are currently available on the use of pomalidomide in combination with EPOCH-R in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
• ECOG performance status 0-4.
• Females of childbearing potential (FCBP) 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 24 hours before starting pomalidomide and must either commit to continued abstinence from heterosexual 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 she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control
• All study participants must agree to be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program.
• Able to take aspirin 81mg orally daily or if intolerant of aspirin, able to take a substitute thromboprophylaxis such as low molecular weight heparin.
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Use of other systemic anticancer treatments or agents within the past 2 weeks (4 weeks if the therapy was a monoclonal antibody)
• Prior dose-adjusted EPOCH or pomalidomide for treatment of KSHV-associated lymphoma
• Parenchymal brain involvement with lymphoma
• History of malignant tumors other than KS or KSHV-associated MCD, unless: In complete remission for greater than or equal to 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
• Inadequate renal function, defined as calculated or estimated creatinine clearance \< 60 mL/min unless lymphoma related
• Inadequate hepatic function:
• Bilirubin (total) \> 1.5 times the upper limit of normal; AST and/or ALT \> 3 times the upper limit of normal; EXCEPTIONS:
• Total bilirubin greater than or equal to 5 mg/dL in patients with Gilbert's syndrome as defined by \>80% unconjugated
• Total bilirubin greater than or equal to 7.5 with direct fraction \> 0.7 if patient is receiving a protease inhibitor at the time of initial evaluation
• Hepatic dysfunction attributed to lymphoma
• ANC \<1000/mm3 and platelets \< 75,000/mm3 unless lymphoma, KSHV-MCD, or KICS- related.
• CTCAEv4.0 Grade 3-4 neuropathy
• Ejection fraction less than 40% by echocardiography

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Related Publications (3)

• Dupin N, Diss TL, Kellam P, Tulliez M, Du MQ, Sicard D, Weiss RA, Isaacson PG, Boshoff C. HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma. Blood. 2000 Feb 15;95(4):1406-12.

  PMID: 10666218 BACKGROUND

• Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, Knowles DM. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood. 1996 Jul 15;88(2):645-56.

  PMID: 8695812 BACKGROUND

• Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995 May 4;332(18):1186-91. doi: 10.1056/NEJM199505043321802.

  PMID: 7700311 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Primary Effusion

Interventions

pomalidomide; Rituximab; Prednisone; Etoposide; Doxorubicin; Vincristine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Thomas S Uldrick, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: August 29, 2014
• Study Start: August 15, 2014
• Primary Completion: May 5, 2015
• Study Completion: May 5, 2015
• Last Updated: August 31, 2018

Record last verified: 2015-05-05