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

Primary Purpose

Lymphoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Lenalidomide

Obinutuzumab

Cyclophosphamide

Doxorubicin

Vincristine

Prednisone

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

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

Inclusion Criteria:

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

Exclusion Criteria:

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)
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.
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.
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

Sites / Locations

University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide + Obinutuzumab + CHOP

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of Lenalidomide, Obinutuzumab, and CHOP

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.

Secondary Outcome Measures

Overall Response Rate

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.

Full Information

NCT ID

NCT02529852

First Posted

August 18, 2015

Last Updated

November 1, 2022

Sponsor

M.D. Anderson Cancer Center

Collaborators

Celgene, Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02529852

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

November 4, 2015 (Actual)

Primary Completion Date

October 31, 2022 (Actual)

Study Completion Date

October 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

Celgene, Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

59 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lenalidomide + Obinutuzumab + CHOP

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Other Intervention Name(s)

CC-5013, Revlimid

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Obinutuzumab

Other Intervention Name(s)

GA101, Gazyva

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan, Neosar

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Other Intervention Name(s)

Doxorubicin Hydrochloride, Adriamycin PFS, Adriamycin RDF, Adriamycin, Rubex

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Vincristine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) of Lenalidomide, Obinutuzumab, and CHOP

Description

Time Frame

21 days

Secondary Outcome Measure Information:

Title

Overall Response Rate

Description

Time Frame

126 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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) 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. 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. 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jason R. Westin, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

36375046

Citation

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.

Results Reference

derived

Links:

URL

http://www.mdanderson.org

Description

University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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