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Lenalidomide and Idelalisib in Treating Patients With Recurrent Follicular Lymphoma

Primary Purpose

Recurrent Follicular Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
idelalisib
lenalidomide
Sponsored by
Alliance for Clinical Trials in Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Follicular Lymphoma focused on measuring recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma

Eligibility Criteria

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

  • Documentation of Disease

    • Previously treated, histologically confirmed follicle center cell lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high-power field with centrocytes present)
    • Bone marrow biopsies as the sole means of diagnosis are not acceptable; fine-needle aspirates are not acceptable for diagnosis
    • Confirmed Cluster of Differentiation 20 (CD20) antigen expression by flow cytometry or immunohistochemistry
  • Measurable disease must be > 1 cm

  • Prior treatment

    • Patient must have had prior treatment with rituximab either alone or in combination with chemotherapy.
    • Last prior treatment regimen need not include rituximab.
    • Patient must have a time to progression of ≥ 6 months from last rituximab dose of last rituximab containing regimen.
    • No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent
  • Patients must be 18 years of age or older.

  • Human immunodeficiency virus (HIV) Infection

    • Patients with HIV infection are eligible, provided they meet the following:
    • CD4+ cell count > 350/mm^3
    • Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3
    • No history of Acquired Immunodeficiency Syndrome (AIDS)-defining conditions or other HIV related illness
    • No concurrent zidovudine or stavudine because of overlapping toxicities with protocol therapy
  • Patients must not have known central nervous system (CNS) involvement
  • Patients must not have known positivity for hepatitis B, as evidenced by + HBsAG or anti-HBc and must not have known history of hepatitis C
  • Patients must not have any currently active secondary malignancy except non-melanoma skin cancer. Patients are not considered to have a "currently active" secondary malignancy if they have completed anticancer therapy and are deemed to have < 30% risk of relapse by their physician.
  • Patients must not have had deep vein thrombosis or pulmonary embolism within the past 3 months.
  • Patients must not have had radioimmunotherapy within 12 months of study entry.
  • Patients must not have other concurrent investigational or commercial agents or therapies for lymphoma.
  • Patients must not have current dialysis treatment.

  • Patients must be non-pregnant and non-nursing.

    • Females of Child Bearing Potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal for at least 24 consecutive months (eg, has had menses at any time preceding 24 consecutive months)
    • FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to registration

    • FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control

      • One highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide
      • FCBP must also agree to ongoing pregnancy testing
    • Men must agree to use a latex condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy

  • CYP3A4 Strong Inducers and Inhibitors

    • Patients must not be on strong CYP3A4 inhibitors and/or inducers.
    • Strong inhibitors are prohibited: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone
    • Strong inducers are prohibited: carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's Wort, troglitazone

  • Required Initial Laboratory Values

    • Absolute neutrophil count (ANC) ≥ 1,000 mm³
    • Total Bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert disease or lymphoma)
    • Creatinine ≤ 1.5 times ULN (unless due to lymphoma) OR creatinine clearance (CrCl) ≤ 60 mL/minute
    • Platelet count ≥ 75,000 mm³
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2 x ULN

Sites / Locations

  • MedStar Georgetown University Hospital
  • University of Chicago
  • Washington University School of Medicine
  • Weill Medical College of Cornell University
  • University of North Carolina at Chapel Hill
  • Ohio State University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

lenalidomide and idelalisib

Arm Description

Lenalidomide: Lenalidomide will be administered orally on days 1-21 followed by 7 days of rest, every 28 days. A treatment cycle will be considered 28 days in length. In the absence of intolerable toxicity or disease progression, lenalidomide will be given for a total of 12 cycles. Idelalisib: Dosing is fixed in all cohorts receiving idelalisib at 150 mg orally (twice daily) for 12 cycles, with the exception of dose modifications for toxicity.

Outcomes

Primary Outcome Measures

MTD based on the incidence of dose-limiting toxicity (DLT) assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Secondary Outcome Measures

Toxicity profile assessed by NCI CTCAE version 4.0
OR rate assessed up to 10 years
CR rate assessed up to 10 years
PFS assessed up to 10 years

Full Information

First Posted
July 17, 2012
Last Updated
January 26, 2018
Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI), Gilead Sciences, Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01644799
Brief Title
Lenalidomide and Idelalisib in Treating Patients With Recurrent Follicular Lymphoma
Official Title
A Phase I Trial of Lenalidomide and Idelalisib in Recurrent Follicular Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI), Gilead Sciences, Celgene Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Biologic therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Idelalisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This phase I trial studies the side effects and the best dose of lenalidomide when giving together with idelalisib in treating patients with recurrent follicular lymphoma.
Detailed Description
OUTLINE: This is a multicenter, dose-escalation study of lenalidomide. Patients receive lenalidomide orally (PO) on days 1-21 and idelalisib twice daily (BID) on days 1-28. Treatment with lenalidomide and idelalisib repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. The primary and secondary objectives of the study include the following: Primary Objective: To determine the maximum-tolerated dose (MTD) of lenalidomide when combined with idelalisib in patients with recurrent follicular non-Hodgkin lymphoma (NHL). Secondary Objectives: To determine the toxicity profile of lenalidomide and idelalisib therapy in patients with recurrent follicular NHL To estimate the efficacy (overall response rate [ORR], complete response rate [CRR], and progression-free survival [PFS]) of lenalidomide and idelalisib in patients with recurrent follicular NHL in a preliminary fashion (using a small extension cohort) To assess whether the therapeutic effects of the lenalidomide and idelalisib combination are sufficiently promising to warrant evaluation in a subsequent (phase II/III) randomized trial After completion of study treatment, patients are followed at 2, 4, 6, 9, 12, 15, 18, and 24 months and then annually. Patients are followed once every year for a maximum of 10 years from study entry.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Follicular Lymphoma
Keywords
recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
lenalidomide and idelalisib
Arm Type
Experimental
Arm Description
Lenalidomide: Lenalidomide will be administered orally on days 1-21 followed by 7 days of rest, every 28 days. A treatment cycle will be considered 28 days in length. In the absence of intolerable toxicity or disease progression, lenalidomide will be given for a total of 12 cycles. Idelalisib: Dosing is fixed in all cohorts receiving idelalisib at 150 mg orally (twice daily) for 12 cycles, with the exception of dose modifications for toxicity.
Intervention Type
Drug
Intervention Name(s)
idelalisib
Intervention Description
oral
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Intervention Description
oral
Primary Outcome Measure Information:
Title
MTD based on the incidence of dose-limiting toxicity (DLT) assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame
Up to 13 months
Secondary Outcome Measure Information:
Title
Toxicity profile assessed by NCI CTCAE version 4.0
Time Frame
Up to 10 years
Title
OR rate assessed up to 10 years
Time Frame
Up to 10 years
Title
CR rate assessed up to 10 years
Time Frame
Up to 10 years
Title
PFS assessed up to 10 years
Time Frame
Up to 10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Documentation of Disease Previously treated, histologically confirmed follicle center cell lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high-power field with centrocytes present) Bone marrow biopsies as the sole means of diagnosis are not acceptable; fine-needle aspirates are not acceptable for diagnosis Confirmed Cluster of Differentiation 20 (CD20) antigen expression by flow cytometry or immunohistochemistry Measurable disease must be > 1 cm Prior treatment Patient must have had prior treatment with rituximab either alone or in combination with chemotherapy. Last prior treatment regimen need not include rituximab. Patient must have a time to progression of ≥ 6 months from last rituximab dose of last rituximab containing regimen. No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent Patients must be 18 years of age or older. Human immunodeficiency virus (HIV) Infection Patients with HIV infection are eligible, provided they meet the following: CD4+ cell count > 350/mm^3 Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3 No history of Acquired Immunodeficiency Syndrome (AIDS)-defining conditions or other HIV related illness No concurrent zidovudine or stavudine because of overlapping toxicities with protocol therapy Patients must not have known central nervous system (CNS) involvement Patients must not have known positivity for hepatitis B, as evidenced by + HBsAG or anti-HBc and must not have known history of hepatitis C Patients must not have any currently active secondary malignancy except non-melanoma skin cancer. Patients are not considered to have a "currently active" secondary malignancy if they have completed anticancer therapy and are deemed to have < 30% risk of relapse by their physician. Patients must not have had deep vein thrombosis or pulmonary embolism within the past 3 months. Patients must not have had radioimmunotherapy within 12 months of study entry. Patients must not have other concurrent investigational or commercial agents or therapies for lymphoma. Patients must not have current dialysis treatment. Patients must be non-pregnant and non-nursing. Females of Child Bearing Potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal for at least 24 consecutive months (eg, has had menses at any time preceding 24 consecutive months) FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to registration FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control One highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide FCBP must also agree to ongoing pregnancy testing Men must agree to use a latex condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy CYP3A4 Strong Inducers and Inhibitors Patients must not be on strong CYP3A4 inhibitors and/or inducers. Strong inhibitors are prohibited: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone Strong inducers are prohibited: carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's Wort, troglitazone Required Initial Laboratory Values Absolute neutrophil count (ANC) ≥ 1,000 mm³ Total Bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert disease or lymphoma) Creatinine ≤ 1.5 times ULN (unless due to lymphoma) OR creatinine clearance (CrCl) ≤ 60 mL/minute Platelet count ≥ 75,000 mm³ Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2 x ULN
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John P. Leonard, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28314699
Citation
Smith SM, Pitcher BN, Jung SH, Bartlett NL, Wagner-Johnston N, Park SI, Richards KL, Cashen AF, Jaslowski A, Smith SE, Cheson BD, Hsi E, Leonard JP. Safety and tolerability of idelalisib, lenalidomide, and rituximab in relapsed and refractory lymphoma: the Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 trials. Lancet Haematol. 2017 Apr;4(4):e176-e182. doi: 10.1016/S2352-3026(17)30028-5. Epub 2017 Mar 15.
Results Reference
derived

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Lenalidomide and Idelalisib in Treating Patients With Recurrent Follicular Lymphoma

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