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

NCT02529852 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2015-0069NCI-2015-01517
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphoma

Keywords

Lymphoma; Diffuse Large B Cell Lymphoma; DLBCL; Lenalidomide; CC-5013; Revlimid; Obinutuzumab; GA101; Gazyva; Cyclophosphamide; Cytoxan; Neosar; Doxorubicin; Doxorubicin Hydrochloride; Adriamycin PFS; Adriamycin RDF; Adriamycin; Rubex; Vincristine; Prednisone

Outcome Measures

Primary Outcomes (1)

• Safety of LO-CHOP

  Assessing the participant's characteristics and clinical outcomes after 2 cycles/42 days of LO-CHOP. The safety evaluation is defined as the lack of any grade ≥3 nonhematologic toxicity unmanageable with aggressive supportive care or toxicity, resulting in a delay of over 7 days of cycle 2.

  up to 42 days

Secondary Outcomes (2)

• Overall Survival

  up to 126 days

• Progression Free Survival

  up to 4.5 years

Study Arms (1)

Lenalidomide + Obinutuzumab + CHOP

EXPERIMENTAL

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; Drug: Obinutuzumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Interventions

Lenalidomide DRUG

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.

Also known as: CC-5013, Revlimid

Lenalidomide + Obinutuzumab + CHOP

Obinutuzumab DRUG

Phase I and II: 1000 mg by vein on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 - 6.

Also known as: GA101, Gazyva

Lenalidomide + Obinutuzumab + CHOP

Cyclophosphamide DRUG

Phase I and II: 750 mg/m2 vein over about 1 hour on Day 1 of all cycles.

Also known as: Cytoxan, Neosar

Lenalidomide + Obinutuzumab + CHOP

Doxorubicin DRUG

Phase I and II: 50 mg/m2 by vein over about 15 minutes each on Day 1 of all cycles.

Also known as: Doxorubicin Hydrochloride, Adriamycin PFS, Adriamycin RDF, Adriamycin, Rubex

Lenalidomide + Obinutuzumab + CHOP

Vincristine DRUG

Phase I and II: 1.4 mg/m2 by vein on Day 1 of all cycles.

Lenalidomide + Obinutuzumab + CHOP

Prednisone DRUG

Phase I and II: 100 mg by mouth daily on Days 1 - 5 of each 21 day cycle.

Lenalidomide + Obinutuzumab + CHOP

Eligibility Criteria

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

You may qualify if:

• 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.
• Measurable disease on cross section imaging that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions
• Appropriate candidate for systemic immune-chemotherapy such as the standard RCHOP21 6 cycles as determined by the treating physician
• Age \>/=18
• 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
• 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.
• 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)
• Consent to potential need for transfusion of blood products
• Able to give informed consent
• Ability and willingness to comply with the requirements of the study protocol

You may not qualify if:

• 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.
• Pregnant or lactating females
• Symptomatic CNS lymphoma involvement
• 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)
• Known HIV or HTLV infection
• Previous malignancy with diagnosis or suspicion of recurrence within the past 2 years, not including non-melanoma skin cancers or in situ malignancies.
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Known hypersensitivity to any of the study drugs
• 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
• Major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• 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.
• 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.
• Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment
• Peripheral neuropathy \>/= Grade 2
• Subjects who are unwilling to take VTE prophylaxis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Cherng HJ, Alig SK, Oki Y, Nastoupil LJ, Fayad L, Neelapu SS, Turturro F, Hagemeister F, Craig AFM, Macaulay CW, Rodriguez MA, Lee HJ, McDonnell TJ, Flowers CR, Vega F, Green MR, Feng L, Kurtz DM, Alizadeh AA, Davis RE, Westin JR. A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL. Blood Adv. 2023 Apr 11;7(7):1137-1145. doi: 10.1182/bloodadvances.2022008174.

  PMID: 36375046 RESULT

• Roschewski M, Kurtz DM, Westin JR, Lynch RC, Gopal AK, Alig SK, Sworder BJ, Cherng HJ, Kuffer C, Blair D, Brown K, Goldstein JS, Schultz A, Close S, Chabon JJ, Diehn M, Wilson WH, Alizadeh AA. Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma. J Clin Oncol. 2025 Dec;43(34):3652-3661. doi: 10.1200/JCO-25-01534. Epub 2025 Aug 13.

  PMID: 40802906 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Lenalidomide; obinutuzumab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Jason Westin
• Organization: M D Anderson Cancer Center

jwestin@mdanderson.org

(713) 792-3750

Study Officials

• Jason R. Westin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 20, 2015
• Study Start: November 4, 2015
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (1)