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

Primary Purpose

Richter's Syndrome, CLL

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Obinutuzumab
lenalidomide
HDMP
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Richter's Syndrome focused on measuring Richter's Syndrome, CLL, Chronic Lumphocytic Leukemia, obinutuzumab, HDMP, lenalidomide, cancer, methylprednisolone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of California, San Diego

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

obinutuzumab, lenalidomide, and HDMP

Arm Description

Outcomes

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
Measured Via Adverse Events

Secondary Outcome Measures

Overall response rate of RS and CLL
Measure via the Cheson Criteria for response in lymphoma.
Progression-free survival rate
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
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)
Measure by percentage of patients able to receive subsequent tell cell transplant

Full Information

First Posted
April 10, 2017
Last Updated
July 1, 2022
Sponsor
University of California, San Diego
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1. Study Identification

Unique Protocol Identification Number
NCT03113695
Brief Title
Obinutuzumab, High Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients With Richter's Syndrome
Official Title
Obinutuzumab, High Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients With Richter's Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
December 20, 2017 (Actual)
Primary Completion Date
May 2, 2022 (Actual)
Study Completion Date
May 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego

4. Oversight

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

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Richter's Syndrome, CLL
Keywords
Richter's Syndrome, CLL, Chronic Lumphocytic Leukemia, obinutuzumab, HDMP, lenalidomide, cancer, methylprednisolone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
obinutuzumab, lenalidomide, and HDMP
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
HDMP
Intervention Description
methylprednisolone 1000 mg/m2 (ie HDMP) on days 1-5 of cycles 1-4
Primary Outcome Measure Information:
Title
Safety and tolerability of the combination of obinutuzumab, lenalidomide, and high dose methylprednisolone in treatments with Richter's Syndrome (RS) measured Via Adverse Events
Description
Measured Via Adverse Events
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall response rate of RS and CLL
Description
Measure via the Cheson Criteria for response in lymphoma.
Time Frame
12 months and 24 months
Title
Progression-free survival rate
Description
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.
Time Frame
12 months and 24 months
Title
Overall survival rate
Description
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.
Time Frame
12 months and 24 months
Title
Patients able to receive a subsequent stem cell transplant (percentage)
Description
Measure by percentage of patients able to receive subsequent tell cell transplant
Time Frame
12 months and 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas J. Kipps, M.D., Ph.D.
Organizational Affiliation
University of California
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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