Expired Study
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Houston, Texas 77030


Purpose:

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 summary:

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.


Criteria:

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 is Available At:


Original ID:

2015-0069


NCT ID:

NCT02529852


Secondary ID:

NCI-2015-01517


Study Acronym:


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


Overall Status:

Active, not recruiting


Study Phase:

Phase 1/Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

M.D. Anderson Cancer Center


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

59


Enrollment Type:

Actual


Overall Contact Information

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

Study Dates

Start Date:November 4, 2015
Completion Date:November 2021
Completion Type:Anticipated
Primary Completion Date:November 2021
Primary Completion Type:Anticipated
Verification Date:May 2019
Last Changed Date:May 14, 2019
First Received Date:August 18, 2015

Study Outcomes

Outcome Type:Primary Outcome
Measure:Maximum Tolerated Dose (MTD) of Lenalidomide, Obinutuzumab, and CHOP
Time Frame:21 days
Safety Issues:False
Description: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 tox
Outcome Type:Secondary Outcome
Measure:Overall Response Rate
Time Frame:126 days
Safety Issues:False
Description: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.

Study Interventions

Intervention Type:Drug
Name:Lenalidomide
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.
Arm Name:Lenalidomide + Obinutuzumab + CHOP
Other Name:CC-5013
Intervention Type:Drug
Name:Obinutuzumab
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.
Arm Name:Lenalidomide + Obinutuzumab + CHOP
Other Name:GA101
Intervention Type:Drug
Name:Cyclophosphamide
Description:Phase I and II: 750 mg/m2 vein over about 1 hour on Day 1 of all cycles.
Arm Name:Lenalidomide + Obinutuzumab + CHOP
Other Name:Cytoxan
Intervention Type:Drug
Name:Doxorubicin
Description:Phase I and II: 50 mg/m2 by vein over about 15 minutes each on Day 1 of all cycles.
Arm Name:Lenalidomide + Obinutuzumab + CHOP
Other Name:Doxorubicin Hydrochloride
Intervention Type:Drug
Name:Vincristine
Description:Phase I and II: 1.4 mg/m2 by vein on Day 1 of all cycles.
Arm Name:Lenalidomide + Obinutuzumab + CHOP
Intervention Type:Drug
Name:Prednisone
Description:Phase I and II: 100 mg by mouth daily on Days 1 - 5 of each 21 day cycle.
Arm Name:Lenalidomide + Obinutuzumab + CHOP

Study Arms

Study Arm Type:Experimental
Arm Name:Lenalidomide + Obinutuzumab + CHOP
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

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:M.D. Anderson Cancer Center
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Celgene

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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