A Phase I/II Study of Lenalidomide and Obinutuzumab With CHOP for Diffuse Large B Cell Lymphoma

November 1, 2022 updated by: M.D. Anderson Cancer Center

There are 2 parts to this study: Part 1 (dose de-escalation) and Part 2 (dose expansion).

The goal of Part 1 of this clinical research study is to find the highest tolerable dose of lenalidomide in combination with obinutuzumab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) that can be given to patients with diffuse large B cell lymphoma.

The goal of Part 2 of this clinical research study is learn if the dose of lenalidomide found in Part 1 can help to control the disease.

The safety of this drug combination will be studied in both parts.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study phase based on when you join this study. Up to 3 groups of up to 6 participants will be enrolled in Phase 1 of the study, and up to 50 participants will be enrolled in Phase 2.

If you are enrolled in Phase 1, the dose of lenalidomide you receive will depend on when you join this study. The first group of participants will receive the highest dose level of lenalidomide. Each new group will receive a lower dose of lenalidomide than the group before it, if intolerable side effects are seen. This will continue until the most tolerable dose of lenalidomide is found.

If you are enrolled in Phase 2, you will receive lenalidomide at the highest dose that was tolerated in Phase 1.

All participants will receive the same dose of CHOP and obinutuzumab.

Study Drug Administration:

Each study cycle is 21 days.

You will take lenalidomide pills by mouth on Days 1-14 of each cycle.

You will receive obinutuzumab by vein over 3-4 hours on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6.

You will receive cyclophosphamide by vein over about 1 hour on Day 1 of all cycles.

You will receive doxorubicin and vincristine by vein over about 15 minutes each on Day 1 of all cycles.

Study Visits:

Within 3 days before Day 1 of Cycles 1-6:

  • You will have a physical exam.
  • Blood (about 8-9 teaspoons) will be drawn for routine tests and to check for PBMCs.

One (1) time each week during Cycle 1 and then at any time the doctor thinks it is needed, blood (about 2-3 teaspoons) will be drawn for routine tests.

At the end of Cycle 1 but before the start of Cycle 2, blood (about 6 teaspoons) will be drawn to check for PBMCs.

At the end of Cycle 3 but before the start of Cycle 4, you will have a PET/CT scan.

If you can become pregnant, blood (about 2-3 teaspoons) will be drawn for a pregnancy test 1 time before Cycle 1 and then 1 time during each cycle after that.

Length of Treatment:

You may receive lenalidomide, obinutuzumab, and CHOP therapy for up to 6 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on this study will be over after follow-up.

End-of-Treatment Visit:

Within 3-4 weeks after your last dose of study drugs:

  • You will have a physical exam.
  • Blood (about 8-9 teaspoons) will be drawn for routine tests and to check for PBMCs.
  • You will have a PET/CT scan.
  • If the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease.
  • If the doctor thinks it is needed and the tumor is accessible, you will have a core needle biopsy to check the status of the disease. To perform a core biopsy, a sample of tissue is removed using a hollow core needle that has a cutting edge.

Follow-Up:

Every 3 months (+/- 4 weeks) during the first year after the End-of-Treatment Visit and then every 4 months (+/- 9 weeks) during the second year:

  • You will have a physical exam.
  • Blood (about 2-3 teaspoons) will be drawn for routine tests.
  • You will have a PET/CT scan.

This is an investigational study. Lenalidomide is FDA approved and commercially available for the treatment of multiple myeloma (MM) and myelodysplastic syndrome (MDS). Obinutuzumab is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). CHOP is FDA approved and commercially available for the treatment of lymphoma and non-Hodgkin's lymphoma.

The combination of lenalidomide, CHOP, and obinutuzumab to treat DLBCL is considered investigational.

Up to 59 participants will be enrolled in this study. All will take part at MD Anderson.

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Confirmed treatment-naïve de novo CD20+ DLBCL, regardless of cell of origin, with Stage II-IV disease, or Stage I disease if 6 cycles of chemotherapy are planned.
  2. Measurable disease on cross section imaging that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions
  3. Appropriate candidate for systemic immune-chemotherapy such as the standard RCHOP21 6 cycles as determined by the treating physician
  4. Age >/=18
  5. Adequate organ function (normal cardiac ejection fraction of >45%, serum bilirubin <1.5 mg/dl, AST or ALT </= 5 x ULN, and creatinine clearance > 30 mL/min (Calculated according to Cockcroft - Gault formula) unless due to lymphoma with documentation of normal function prior to onset of lymphoma. In the case of Gilberts Syndrome, or documented liver or pancreatic involvement by lymphoma, the requirement for total bilirubin is </=5.0 mg/dl
  6. ANC >1000/mm3, hemoglobin >8.0, and platelets >100,000/mm3. If bone marrow is involved with lymphoma and normal marrow function prior to onset of lymphoma is documented: ANC of >750, any hemoglobin, and platelets of >50,000/mm3.
  7. Performance status <3 (unless previous performance status was 0 or 1 and deterioration is due to lymphoma which treating MD expects to reverse with therapy)
  8. Consent to potential need for transfusion of blood products
  9. Able to give informed consent
  10. Ability and willingness to comply with the requirements of the study protocol

Exclusion Criteria:

  1. Prior history of low grade lymphoma with transformation to DLBCL. If a patient has a composite diagnosis of DLBCL and low grade without a prior history of lymphoma, they will not be considered ineligible.
  2. Pregnant or lactating females
  3. Symptomatic CNS lymphoma involvement
  4. Significant comorbidity (cirrhosis, severe coronary artery disease, significant psychiatric illness, or other that may compromise the ability to safely administer the therapy at the discretion of the primary investigator)
  5. HBV: Patients with positive serology for Hepatitis B defined as positivity for HBsAg or anti-HBc. Patients who are positive for anti-HBc may be considered for inclusion in the study on a case-by-case basis if they are hepatitis B viral DNA negative and are willing to undergo ongoing HBV DNA testing by real-time PCR. Patients with positive serology may be referred to a hepatologist or gastroenterologist for appropriate monitoring and management.
  6. Hepatitis C (HCV): Patients with positive hepatitis C serology unless HCV RNA is confirmed negative and may be considered for inclusion in the study on a case-by-case basis.
  7. Known HIV or HTLV infection
  8. Previous malignancy with diagnosis or suspicion of recurrence within the past 2 years, not including non-melanoma skin cancers or in situ malignancies.
  9. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  10. Known hypersensitivity to any of the study drugs
  11. 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 Cycle 1
  12. Major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
  13. Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly.
  14. Effective contraception is required while receiving obinutuzumab. For women, effective contraception is required to continue for >/= 12 months after the last dose of obinutuzumab. For men, effective contraception is required to continue for 3 months after the last dose of obinutuzumab treatment.
  15. Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment
  16. Peripheral neuropathy >/= Grade 2
  17. Subjects who are unwilling to take VTE prophylaxis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lenalidomide + Obinutuzumab + CHOP

Phase I: Participants take Lenalidomide by mouth on Days 1 - 14 of each cycle. Participants receive Obinutuzumab by vein over 3 - 4 hours on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 - 6. Participants receive Cyclophosphamide by vein over about 1 hour on Day 1 of all cycles. Participants receive Doxorubicin and Vincristine by vein over about 15 minutes each on Day 1 of all cycles.

Phase II: Participants treated at the recommended phase II dosing (RP2D) of Lenalidomide determined in the Phase Ib portion for 6 cycles of therapy. Dose of Obinutuzumab, Cyclophosphamide, Doxorubicin and Vincristine remain the same as in Phase I.

Each study cycle is 21 days.
Drug: Lenalidomide

Phase I Starting Dose Level: 15 mg by mouth on Days 1 - 14 of each 21 day cycle.

Phase II Starting Dose Level: Maximum tolerated dose from Phase I.

Other Names:
  • CC-5013
  • Revlimid
Drug: Obinutuzumab
Phase I and II: 1000 mg by vein on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 - 6.
Other Names:
  • Gazyva
  • GA101
Drug: Cyclophosphamide
Phase I and II: 750 mg/m2 vein over about 1 hour on Day 1 of all cycles.
Other Names:
  • Cytoxan
  • Neosar
Drug: Doxorubicin
Phase I and II: 50 mg/m2 by vein over about 15 minutes each on Day 1 of all cycles.
Other Names:
  • Adriamycin
  • Adriamycin PFS
  • Adriamycin RDF
  • Rubex
  • Doxorubicin Hydrochloride
Drug: Vincristine
Phase I and II: 1.4 mg/m2 by vein on Day 1 of all cycles.
Drug: Prednisone
Phase I and II: 100 mg by mouth daily on Days 1 - 5 of each 21 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of Lenalidomide, Obinutuzumab, and CHOP
Time Frame: 21 days
MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). DLT defined as grade ≥ 3 non-hematologic toxicity per NCI CTCAE 4.0 unmanageable with aggressive supportive care or toxicity resulting in a delay of over 7 days of cycle 2.
21 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 126 days
Overall response rate defined as the proportion of subjects who have achieved either complete response (CR) or partial response (PR) prior to any treatment change. Evaluation made by end of treatment and subsequent follow up PET/CT scans.
126 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Genentech, Inc.
Celgene

Investigators

  • Principal Investigator: Jason R. Westin, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 4, 2015

Primary Completion (Actual)

October 31, 2022

Study Completion (Actual)

October 31, 2022

Study Registration Dates

First Submitted

August 18, 2015

First Submitted That Met QC Criteria

August 18, 2015

First Posted (Estimate)

August 20, 2015

Study Record Updates

Last Update Posted (Actual)

November 3, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-0069
  • NCI-2015-01517 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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