Obinutuzumab, High Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients With Richter's Syndrome

Sponsor

University of California, San Diego (Other)

Overall Status

Completed

CT.gov ID

NCT03113695

Collaborator

(none)

Enrollment

Location

Arm

52.4

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to investigate whether combination of obinutuzumab, lenalidomide, and high dose methylprednisolone in the treatment of Richter's Syndrome. The study will evaluate whether this regimen can reduce the amount of cancerous cells in your body. All of these agents are approved by the FDA Obinutuzumab is a protein molecule manufactured from a single cell population, has been approved by the Food and Drug Administration (FDA) for the treatment of CLL of SLL. Lenalidomide is for the treatment of patients with other blood cancers. Methylprednisolone is a type of steroid, and it is used in a wide variety of medical conditions. These agents and the combination of these agents are not approved for the treatment of Richter's Syndrome and are considered experimental.

Condition or Disease	Intervention/Treatment	Phase
Richter's Syndrome CLL	Drug: Obinutuzumab Drug: lenalidomide Drug: HDMP	Phase 1

Detailed Description

This is a phase I trial to determine the safety and tolerability of the combination of obinutuzumab, lenalidomide, and HDMP for patients with RS. There is not a standard of care for patients with Richter's Syndrome (RS). Ten patients will be enrolled with RS diagnosed by histology or flow cytometry and CLL, regardless of prior treatment for either condition.

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Obinutuzumab, High Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients With Richter's Syndrome

Actual Study Start Date :

Dec 20, 2017

Actual Primary Completion Date :

May 2, 2022

Actual Study Completion Date :

May 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: obinutuzumab, lenalidomide, and HDMP	Drug: Obinutuzumab obinutuzumab 1000 mg x 8 doses (first dose split on Cycle 1 days 1 100mg and 2 900mg; then day 8 and 15 of cycle 1; then day 1 of cycles 2-6, each cycle being 28 days long) Drug: lenalidomide lenalidomide PO daily. The starting dose of lenalidomide is 5 mg PO daily. Starting on C2D1, the dose increases every 2 weeks in 5 mg increments to a maximum of 25 mg PO daily. Patients will continue lenalidomide until disease progression, unacceptable toxicity, or subsequent therapy. Drug: HDMP methylprednisolone 1000 mg/m2 (ie HDMP) on days 1-5 of cycles 1-4

Arm

Intervention/Treatment

Experimental: obinutuzumab, lenalidomide, and HDMP

Drug: Obinutuzumab

obinutuzumab 1000 mg x 8 doses (first dose split on Cycle 1 days 1 100mg and 2 900mg; then day 8 and 15 of cycle 1; then day 1 of cycles 2-6, each cycle being 28 days long)

Drug: lenalidomide

lenalidomide PO daily. The starting dose of lenalidomide is 5 mg PO daily. Starting on C2D1, the dose increases every 2 weeks in 5 mg increments to a maximum of 25 mg PO daily. Patients will continue lenalidomide until disease progression, unacceptable toxicity, or subsequent therapy.

Drug: HDMP

methylprednisolone 1000 mg/m2 (ie HDMP) on days 1-5 of cycles 1-4

Outcome Measures

Primary Outcome Measures

Safety and tolerability of the combination of obinutuzumab, lenalidomide, and high dose methylprednisolone in treatments with Richter's Syndrome (RS) measured Via Adverse Events [2 years]
Measured Via Adverse Events

Secondary Outcome Measures

Overall response rate of RS and CLL [12 months and 24 months]
Measure via the Cheson Criteria for response in lymphoma.
Progression-free survival rate [12 months and 24 months]
Measure via the Cheson Criteria for response in lymphoma. PFS is defined as the time from entry onto a study until lymphoma progression or death as a result of any cause.
Overall survival rate [12 months and 24 months]
Measure via the Cheson Criteria for response in lymphoma. Defined as the time from entry onto the clinical trial until death as a result of any cause.
Patients able to receive a subsequent stem cell transplant (percentage) [12 months and 24 months]
Measure by percentage of patients able to receive subsequent tell cell transplant

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologic diagnosis of Richter's Syndrome (RS)
No requirement nor restriction for prior therapy or stage
Measurable disease: may include FDG avid lesion, lymph node greater than 1.5 cm in greatest diameter, or clonal large B-cells in peripheral blood or bone marrow.
ECOG 0-2
Adequate organ function
Adequate bone marrow function

Lenalidomide-related inclusion criteria:

Able to take aspirin (81mg or 325mg) daily, warfarin, low molecular weight heparin, or equivalent anticoagulation as prophylactic medication.
All study participants must be registered into the mandatory REVLIMID REMS® program, and be willing and able to comply with the requirements of REMS®.
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours prior to starting REVLIMID® 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 REVLIMID®. FCBP must also agree to ongoing pregnancy testing.
Males must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

Exclusion Criteria:

History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
Known hypersensitivity to any of the study drugs
Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for 2 years prior to enrollment.
Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of treatment
Major surgery within 4 weeks prior to the start of treatment
Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1) seropositive status
Positive hepatitis serology
Women who are pregnant or lactating
Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment
Uncontrolled diabetes mellitus
Myocardial infarction within 6 months of starting study drug
Other clinically significant heart disease