Rituximab + High-Dose Methylprednisolone Debulking Prior to Venetoclax for CLL & SLL Patients

NCT04981912 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 182029
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate whether the combination of rituximab and high dose methylprednisolone can be given together, can reduce the amount of cancer cells that are present prior to starting venetoclax, and therefore make it safer to take venetoclax. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) will be treated in this study. Subjects will be assessed for their risk of tumor lysis syndrome (TLS), a potentially serious side effect associated with venetoclax and rituxan. TLS is caused by the fast breakdown of cancer cells. TLS can lead to kidney failure or abnormal heart rhythm. Depending on their TLS risk, patients will be assigned to one of two treatment arms. Patients who are at high risk for TLS at baseline will receive HDMP/Rituximab for 1 cycle before beginning venetoclax. Patients who are at low risk for TLS at baseline will not receive HDMP/Rituximab and will instead start directly with venetoclax. Once the proper dose of venetoclax is reached, both arms will continue venetoclax for up to 2 years and receive rituximab for 5 cycles. The purpose is to determine if HDMP/Rituximab prior to venetoclax is efficient at reducing tumor burden and lowering the risk of developing TLS. Although all of these drugs are approved by the FDA for the treatment of patients with CLL or SLL, and although the combination of rituximab and venetoclax is approved by the FDA for the treatment of patients with CLL or SLL, the combination and dosing schedule in this trial are considered experimental.

Conditions

Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients That Have a Decrease in Tumor Burden From Medium or High to Low

  Percentage of patients that have a decrease in tumor burden from levels of disease that meet "Medium/High-tumor burden" criteria to meet "Low tumor burden" criteria for disease burden following 1 or 2 cycles of HDMP + Rituximab. Low Tumor Burden = All measurable lymph nodes with the largest diameter \< 5 cm by radiologic assessment AND ALC \< 25k/uL Medium Tumor Burden = Any measurable lymph node with the largest diameter \>/= 5 cm but \< 10 cm by radiographic assessment OR ALC \>/= 25k/uL High Tumor Burden = Any measurable lymph node with the largest diameter \>/= 10 cm by radiologic assessment OR ALC \>/= 25k/uL AND any measurable lymph node with the largest diameter \>/= 5 cm

  28 or 56 days

Secondary Outcomes (7)

• Percentage of Patients That Have a Decrease in Tumor Burden From Medium to Low

  3 years

• Percentage of Patients That Have a Decrease in Tumor Burden if 2 Cycles of HDMP + Rituximab

  56 days

• Rate of Laboratory TLS (Tumor Lysis Syndrome)

  2.15 years

• Rate of Clinical TLS

  2.15 years

• Adverse Events by CTCAE4 Definitions

  2.15 years

Study Arms (1)

Arm A

EXPERIMENTAL

HDMP + rituximab as a means of debulking prior to initiating venetoclax.

Drug: HDMP + rituximab as a means of debulking prior to initiating venetoclax.

Interventions

HDMP + rituximab as a means of debulking prior to initiating venetoclax. DRUG

* Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden, * If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert. * Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.

Also known as: Methylnaphthidate + Riabni/Rituxan/Ruxience/Truxima

Arm A

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria for study entry:
• Subjects must be age 18 or older.
• Both men and women of all races and ethnic groups are eligible for this trial.
• Ability to understand and willingness to sign a written informed consent.
• Diagnosis: CLL or SLL, as documented in the medical record
• Disease Status/ Prior Therapy:
• Must have had treatment for CLL/SLL with at least 1 line of prior therapy. (There is not requirement nor restriction for specific type of previous therapy, with the following exceptions: prior treatment with venetoclax within 6 months, prior progressive disease on venetoclax, or prior grade 3 or 4 toxicity (not including TLS) that directly lead to discontinuation of venetoclax; Prior HDMP/Rituximab is allowed unless there was no response (Stable Disease or Progressive Disease) or was within 3 months.)
• Indication for CLL or SLL therapy based on international working group (iwCLL) guidelines, which include: constitutional symptoms, bulky or symptomatic lymphadenopathy, bulky or symptomatic splenomegaly, rapid doubling of the ALC (approximately 6 months or less), or Rai stage 3 or 4 disease.
• Disease burden meets criteria for Medium or High Tumor Burden, based on Absolute lymphocyte count \>/= 25k/uL or any lymph node 5 cm or greater in diameter. The ALC criteria must be met during the screening period. The imaging criteria may be based on radiologic study within 30 days of Cycle 0, Day 1.
• Has recovered from the toxic effects of prior therapy to their clinical baseline.
• Women of child-bearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree to not become pregnant for the duration of the study. Both men and women must agree to use a barrier method of contraception for the duration of the study and until 5 half-lives after the final dose of venetoclax (approximately 1 week), and at least 5 half-lives of final dose of Rituximab.
• ECOG performance status of 0-2
• Adequate hematologic function: Platelet count \>/= 30k/uL, hemoglobin \> 7 g/dL, AND ANC \> 500/uL. (Values may be lower if due to marrow infiltration by CLL).
• Adequate renal function: creatinine clearance based on 24 hr collection \>/= 40 ml/min; OR Calculated Creatinine clearance (CrCl) ≥ 40 mL/min (based upon the Cockcroft-Gault Equation \[CrCl = (140-age) \* actual wt (in kg) \* (0.85 if female) / (72 \* Cr)\].
• Adequate hepatic function:

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Subject is known to be positive for HIV. (HIV testing is not required.)
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
• Treatment with any of the following within 7 days prior to the first dose of venetoclax:
• Steroid therapy for anti-neoplastic intent
• moderate or strong cytochrome P450 3A (CYP3A) inhibitors (see Appendix C for examples)
• moderate or strong CYP3A inducers (see Appendix C for examples)
• Administration or consumption of any of the following within 3 days prior to the first dose of venetoclax:
• grapefruit or grapefruit products
• Seville oranges (including marmalade containing Seville oranges)
• star fruit
• Prior CLL therapy:
• Biologic agent (monoclonal antibody) within 30 days for anti-neoplastic intent.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Michael Choi
• Organization: UCSD

mychoi@ucsd.edu

8585341765

Study Officials

• Choi Michael, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 29, 2021
• Study Start: September 2, 2021
• Primary Completion: July 22, 2025
• Study Completion (Estimated): July 22, 2026
• Last Updated: October 15, 2025
• Results First Posted: October 15, 2025

Record last verified: 2025-09

Locations

US (1)