Clinical Trials /

Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

NCT01896999

Description:

This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a combining monoclonal antibody with an anticancer drug that binds to a protein on the surface of lymphoma cells called cluster of differentiation (CD)30 and may kill the cells. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
  • Official Title: A Phase I Study With an Expansion Cohort/Randomized Phase II Study of the Combinations of Ipilimumab, Nivolumab, and Brentuximab Vedotin in Patients With Relapsed/Refractory Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2013-01275
  • SECONDARY ID: NCI-2013-01275
  • SECONDARY ID: E4412
  • SECONDARY ID: E4412
  • SECONDARY ID: E4412
  • SECONDARY ID: U10CA180820
  • SECONDARY ID: U24CA196172
  • NCT ID: NCT01896999

Conditions

  • Classical Hodgkin Lymphoma
  • Recurrent Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Brentuximab VedotinADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35Arm I (brentuximab vedotin, nivolumab)
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyArm II (brentuximab vedotin, nivolumab, ipilimumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm I (brentuximab vedotin, nivolumab)

Purpose

This randomized phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin in treating patients with Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Monoclonal antibodies, such as ipilimumab and nivolumab, may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a combining monoclonal antibody with an anticancer drug that binds to a protein on the surface of lymphoma cells called cluster of differentiation (CD)30 and may kill the cells. It is not know whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the
      combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and
      brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate the complete
      response (CR) rate for the regimens of brentuximab vedotin and nivolumab compared to
      brentuximab vedotin, ipilimumab, and nivolumab. (Phase II)

      SECONDARY OBJECTIVES:

      I. To evaluate complete response (CR) rate, partial response (PR) rate and overall response
      rate (ORR), for the combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin
      and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate
      the duration of remission (DOR) to these combinations and compare with the DOR achieved with
      the most recent prior systemic therapy. (Phase I) III. To evaluate the progression-free
      survival (PFS) and the overall survival (OS) in patients receiving the combination of
      brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab
      vedotin, ipilimumab, and nivolumab. (Phase I) IV. To evaluate the ORR, PR, and stable disease
      (SD) rate for the combinations of brentuximab vedotin and nivolumab and brentuximab vedotin,
      ipilimumab, and nivolumab. (Phase II) V. To evaluate the DOR to these combinations and
      compare with the DOR achieved with the most recent prior systemic therapy. (Phase II) VI. To
      evaluate the 5 year PFS and OS in patients receiving the combinations of brentuximab vedotin
      and nivolumab and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II) VII. To further
      evaluate the safety and characterize the toxicity for the combinations of brentuximab vedotin
      and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II)

      TERTIARY OBJECTIVES:

      I. To evaluate the ability of these combinations to alter tumor specific T cell immunity.
      (Phase I) II. To evaluate the effects of these combinations on systemic immunity. (Phase I)
      III. To evaluate a panel of cytokine and T cell specific biomarkers from the peripheral blood
      as a potential immune signature of treatment response to therapy with these combinations for
      patients with relapsed/refractory Hodgkin lymphoma (HL). (Phase I) IV. To evaluate using gene
      expression profiling (GEP) a signature of response to these novel combinations of an antibody
      drug conjugate with immunomodulatory therapy. (Phase I) V. To evaluate the ability of these
      combinations to alter tumor specific T cell immunity, and circulating T cell phenotypes, in
      patients as a function of treatment response at multiple timepoints during therapy. (Phase
      II) VI. To evaluate peripheral blood cytokine profiles in responding and resistant patients
      at multiple timepoints during therapy. (Phase II) VII. To evaluate using GEP a signature of
      response versus (vs.) resistance to these novel combinations of an antibody drug conjugate
      with immunomodulatory therapy. (Phase II)

      OUTLINE: This is a dose-escalation study of ipilimumab and nivolumab followed by a phase II
      study. Patients are randomized into 1 of 2 arms.

      ARM I: Patients receive brentuximab vedotin intravenously (IV) over 90 minutes and nivolumab
      IV over 30 minutes on day 1. Treatment of brentuximab vedotin repeats every 21 days for up to
      16 courses and treatment of nivolumab repeats every 21 days for up to 34 courses in the
      absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of courses 1-16,
      nivolumab IV over 30 on day 1 of courses 1-34, and ipilimumab IV over 30 minutes on day 1 of
      courses 1, 5, 9, and 13 and then every 12 weeks for up to 8 doses. Courses repeat every 21
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, Phase I patients are followed up periodically for 3
      years, and Phase II patients are followed up for 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (brentuximab vedotin, nivolumab)ExperimentalPatients receive brentuximab vedotin IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment of brentuximab vedotin repeats every 21 days for up to 16 courses and treatment of nivolumab repeats every 21 days for up to 34 courses in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
Arm II (brentuximab vedotin, nivolumab, ipilimumab)ExperimentalPatients receive brentuximab vedotin IV over 90 minutes on day 1 of courses 1-16, nivolumab IV over 30 on day 1 of courses 1-34, and ipilimumab IV over 30 minutes on day 1 of courses 1, 5, 9, and 13 and then every 12 weeks for up to 8 doses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin

Eligibility Criteria

        Inclusion Criteria:

          -  PHASE I: Patients must have pathologically confirmed relapsed or refractory classical
             Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies
             including lymphocyte predominant (LP) HL are not permitted

          -  PHASE I: Patients must have relapsed after first line chemotherapy; may have relapsed
             after autologous or allogeneic stem cell transplant, or have primary refractory
             disease; no upper limit for number of prior therapies; if status post allogeneic stem
             cell transplant, no active graft versus host disease

          -  PHASE I: Patients may have received prior brentuximab vedotin, but must not have
             received brentuximab vedotin within 6 months prior to registration, and must not have
             relapsed within 6 months of receiving previous brentuximab vedotin; patients may not
             have received prior nivolumab or programmed cell death protein 1 (PD1)/programmed cell
             death ligand 1 (PDL1) axis agents; patients in the nivolumab/brentuximab cohorts ONLY
             (D, E, F, Y) may have received prior ipilimumab

          -  PHASE I: Patients may have received other prior activating immunotherapies (i.e.
             checkpoint inhibitors), but must not have received them within 6 months prior to
             registration, and there must be no serious unresolved complication of therapy at the
             time of registration; for the purposes of this study monoclonal antibodies and
             antibody drug conjugates are not considered to be activating immunotherapies and there
             are no additional time restrictions on prior exposure to these agents (except prior
             brentuximab vedotin)

          -  PHASE I: Eastern Cooperative Oncology Group (ECOG)-American College of Radiology
             Imaging Network (ACRIN) performance status between 0-2

          -  PHASE I: Patients must have measurable disease; baseline measurements and evaluations
             must be obtained within 4 weeks of registration to the study; abnormal positron
             emission tomography (PET) scans will not constitute evaluable disease unless verified
             by a diagnostic quality computed tomography (CT) scan; patients must use the same
             imaging modality (CT or PET/CT) throughout the study

          -  PHASE I: Women must not be pregnant or breast-feeding; all females of childbearing
             potential must have a blood test or urine study within 2 weeks prior to registration
             to rule out pregnancy; a female of childbearing potential is any woman, regardless of
             sexual orientation or whether they have undergone tubal ligation, who meets the
             following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or
             2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has
             had menses at any time in the preceding 24 consecutive months)

          -  PHASE I: Women of childbearing potential (WOCBP) and sexually active males must either
             abstain from sexual intercourse for the duration of their participation in the study
             or agree to use both double barrier contraception and birth control pills or implants
             for at least one week prior to the start of the study drug and continuing for a period
             of 5 months after the last dose of study drug (for female patients) and for 7 months
             after the last dose of study drug (for male patients who are sexually active with
             WOCBP)

          -  PHASE I: Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she (or the participating partner) should
             inform the treating physician immediately

          -  PHASE I: Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92%
             while breathing room air

          -  PHASE I: Patients must have forced expiratory volume in one second (FEV1)/forced vital
             capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal
             mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50%
             predicted value; all pulmonary function tests must be obtained within one month prior
             to registration

          -  PHASE I: Absolute neutrophil count (ANC) >= 1500/mcL (1.5 x 10^9/L)

          -  PHASE I: Platelets >= 75,000/mcL (75 x 10^9/L)

          -  PHASE I: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x
             upper limit of normal (ULN)

          -  PHASE I: Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's
             syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted)

          -  PHASE I: Calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min

          -  PHASE I: No evidence of prior malignancy except adequately treated non-melanoma skin
             cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy
             continuously disease free for >= 5 years so as not to interfere with interpretation of
             radiographic response

          -  PHASE I: Patient must have no current or prior history of central nervous system (CNS)
             involvement

          -  PHASE I: All prior therapy must have been completed at least 21 days prior to
             enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids
             for the purpose of treatment of lymphoma are allowed; topical steroids are allowed

          -  PHASE I: No history of Steven's Johnson's syndrome, toxic epidermal necrolysis (TENs)
             syndrome, or motor neuropathy

          -  PHASE I: Human immunodeficiency virus (HIV) positive patients are allowed on this
             study if they have a cluster of differentiation 4 (CD4) count > 400, and are on a
             stable antiviral regimen; patients with poorly controlled HIV or other chronic active
             viral infections will be excluded

          -  PHASE I: Patients must not have autoimmune disorders or conditions of
             immunosuppression that require current ongoing treatment with systemic corticosteroids
             (or other systemic immunosuppressants), including oral steroids (i.e., prednisone,
             dexamethasone) or continuous use of topical steroid creams or ointments or
             ophthalmologic steroids; a history of occasional (but not continuous) use of steroid
             inhalers is allowed

               -  Replacement doses of steroids for patients with adrenal insufficiency are
                  allowed; patients who discontinue use of these classes of medication for at least
                  2 weeks prior to randomization are eligible if, in the judgment of the treating
                  physician investigator, the patient is not likely to require resumption of
                  treatment with these classes of drugs during the study

               -  Exclusion from this study also includes patients with a history of symptomatic
                  autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis
                  [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune
                  vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of
                  autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis); other
                  CNS autoimmune disease (e.g., multiple sclerosis); patients with autoimmune
                  hypothyroid disease or type I diabetes on replacement treatment are eligible

          -  PHASE I: Patients must not have grade 2 or greater peripheral sensory neuropathy

          -  PHASE I: Patients must not have New York Heart Association (NYHA) class III or IV
             heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
             electrocardiographic evidence of acute ischemia

          -  PHASE I: Patients must not have previously existing hypersensitivity to brentuximab
             vedotin or ipilimumab

          -  PHASE I: Patients must not have a serious medical or psychiatric illness likely to
             interfere with study participation

          -  PHASE I: Patients must not be participating in any other clinical trial or taking any
             other experimental medications within 21 days prior to registration

          -  PHASE I: Routine vaccination, including seasonal influenza, should be given at least 2
             weeks prior to study treatment; vaccines are not prohibited on study, but must be
             given at least 6 weeks after cycle 1 and not within 7 days of treatment

          -  PHASE I: Patients registering to arms D, E, F, G, H, I, X, Y must not currently be
             smoking tobacco or other substances and must not have smoked within the past 6 months

          -  PHASE II: Patients must have pathologically confirmed relapsed or refractory classical
             Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies
             including lymphocyte predominant (LP) HL are not permitted

          -  PHASE II: Patients must have relapsed after first line chemotherapy; may have relapsed
             after autologous or allogeneic stem cell transplant, or have primary refractory
             disease; no upper limit for number of prior therapies; if status post allogeneic stem
             cell transplant, no active graft versus host disease and not on immunosuppressive
             therapy

          -  PHASE II: Patients may have received prior brentuximab vedotin, but must not have
             received brentuximab vedotin within 6 months prior to registration, and must not have
             relapsed within 6 months of receiving previous brentuximab vedotin; patients may not
             have received prior nivolumab or PD1/PDL1 axis agents; patients may not have received
             prior ipilimumab

          -  PHASE II: Patients may have received other prior activating immunotherapies, but must
             not have received them within 6 months prior to registration, and there must be no
             serious unresolved complication of therapy at the time of registration; for the
             purposes of this study monoclonal antibodies and antibody drug conjugates are not
             considered to be activating immunotherapies and there are no additional time
             restrictions on prior exposure to these agents (except prior brentuximab vedotin)

          -  PHASE II: ECOG-ACRIN performance status between 0-2

          -  PHASE II: Patients must have measurable disease; baseline measurements and evaluations
             must be obtained within 4 weeks of registration to the study; abnormal PET scans will
             not constitute evaluable disease unless verified by a diagnostic quality CT scan;
             patients must use the same imaging modality (CT or PET/CT) throughout the study

          -  PHASE II: Women must not be pregnant or breast-feeding; all females of childbearing
             potential must have a blood test or urine study within 2 weeks prior to registration
             to rule out pregnancy; a female of childbearing potential is any woman, regardless of
             sexual orientation or whether they have undergone tubal ligation, who meets the
             following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or
             2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has
             had menses at any time in the preceding 24 consecutive months)

          -  PHASE II: Women of childbearing potential (WOCBP) and sexually active males must
             either abstain from sexual intercourse for the duration of their participation in the
             study or agree to use both double barrier contraception and birth control pills or
             implants for at least one week prior to the start of the study drug and continuing for
             5 months after the last dose of study drug (for female patients) and for 7 months
             after the last dose of study drug (for male patients who are sexually active with
             WOCBP); should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she (or the participating partner) should
             inform the treating physician immediately

          -  PHASE II: Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92%
             while breathing room air

          -  PHASE II: Patients must have FEV1/FVC > 60% by pulmonary function test (PFT), unless
             due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO),
             FEV1, and FVC all >50% predicted value; all pulmonary function tests must be obtained
             within one month prior to registration

          -  PHASE II: ANC >= 1500/mcL (1.5 x 10^9/L)

          -  PHASE II: Platelets >= 75,000/mcL (75 x 10^9/L)

          -  PHASE II: AST/ALT =< 2.5 x upper limit of normal (ULN)

          -  PHASE II: Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's
             syndrome, for which Bilirubin =< 3 x upper limit of normal (ULN) is permitted)

          -  PHASE II: Calculated creatinine clearance by Cockroft-Gault formula >= 30 ml/min

          -  PHASE II: No evidence of prior malignancy except adequately treated non-melanoma skin
             cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy
             continuously disease free for >= 5 years so as not to interfere with interpretation of
             radiographic response

          -  PHASE II: Patient must have no current or prior history of CNS involvement

          -  PHASE II: All prior therapy must have been completed at least 21 days prior to
             enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids
             for the purpose of treatment of lymphoma are allowed; topical steroids are allowed

          -  PHASE II: No history of Steven's Johnson's syndrome, TENs syndrome, or motor
             neuropathy

          -  PHASE II: HIV positive patients are allowed on this study if they have a CD4 count >
             400, and are on a stable antiviral regimen; patients with poorly controlled HIV or
             other chronic active viral infections will be excluded

          -  PHASE II: Patients must not have autoimmune disorders or conditions of
             immunosuppression that require current ongoing treatment with systemic corticosteroids
             (or other systemic immunosuppressants), including oral steroids (i.e., prednisone,
             dexamethasone) or continuous use of topical steroid creams or ointments or
             ophthalmologic steroids; a history of occasional (but not continuous) use of steroid
             inhalers is allowed; replacement doses of steroids for patients with adrenal
             insufficiency are allowed; patients who discontinue use of these classes of medication
             for at least 2 weeks prior to randomization are eligible if, in the judgment of the
             treating physician investigator, the patient is not likely to require resumption of
             treatment with these classes of drugs during the study

          -  PHASE II: Patients with a history of symptomatic autoimmune disease (e.g., rheumatoid
             arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus,
             Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor
             neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and
             myasthenia gravis); other CNS autoimmune disease (e.g., multiple sclerosis)

          -  PHASE II: Patients with autoimmune hypothyroid disease or type I diabetes on
             replacement treatment are eligible

          -  PHASE II: Patients must not have grade 2 or greater peripheral sensory neuropathy

          -  PHASE II: Patients must not have NYHA Class III or IV heart failure, uncontrolled
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
             of acute ischemia

          -  PHASE II: Patients must not have previously existing hypersensitivity to brentuximab
             vedotin or ipilimumab

          -  PHASE II: Patients must not have a serious medical or psychiatric illness likely to
             interfere with study participation

          -  PHASE II: Patients must not be participating in any other clinical trial or taking any
             other experimental medications within 21 days prior to registration

          -  PHASE II: Routine vaccinations, including seasonal influenza, should be given at least
             2 weeks prior to study treatment; vaccines are not prohibited on study, but must be
             given at least 6 weeks after cycle 1 and not within 7 days of treatment

          -  PHASE II: Patients must not cur
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete response (CR) rate (Phase II)
Time Frame:Up to 5 years
Safety Issue:
Description:The analysis of CR between two arms will be performed using Cochran-Mantel-Haenszel (CMH) test stratifying on prior BV (Yes versus [vs.] No). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.

Secondary Outcome Measures

Measure:Complete response (CR) rate, assessed using the Revised Response Criteria for Malignant Lymphoma (Cheson et al.) (Phase I)
Time Frame:Up to 3 years
Safety Issue:
Description:Reported along with the 95% CI.
Measure:Duration of response (DOR) (Phase I)
Time Frame:From the documented beginning of response (CR or PR) to the time of relapse, assessed up to 3 years
Safety Issue:
Description:DOR will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates. Descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy.
Measure:Duration of response (DOR) (Phase II)
Time Frame:From the documented beginning of response (CR or PR) to the time of relapse, assessed up to 5 years
Safety Issue:
Description:DOR will also be estimated using Kaplan-Meier methodology. The DOR achieved with the most recent prior systemic therapy will be collected on the case report forms (CRFs), and descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy.
Measure:Overall response rate (ORR) assessed using Revised Response (Cheson) and Deauville criteria (Phase II)
Time Frame:Up to 5 years
Safety Issue:
Description:The analysis of ORR between two arms will be performed using Cochran-Mantel-Haenszel (CMH) test stratifying on prior BV (Yes Vs. No). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
Measure:Overall response rate (ORR) rate, assessed using the Revised Response Criteria for Malignant Lymphoma (Cheson et al.) (Phase I)
Time Frame:Up to 3 years
Safety Issue:
Description:Reported along with the 95% CI.
Measure:Overall survival (OS) (Phase I)
Time Frame:From the date of study entry to the date of death, assessed up to 3 years
Safety Issue:
Description:OS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.
Measure:Overall survival (OS) (Phase II)
Time Frame:From randomization to death from any cause, assessed up to 5 years
Safety Issue:
Description:Will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome.
Measure:Partial response (PR) rate, assessed using the Revised Response Criteria for Malignant Lymphoma (Cheson et al.) (Phase I)
Time Frame:Up to 3 years
Safety Issue:
Description:Reported along with the 95% CI.
Measure:Progression free survival (PFS) (Phase II)
Time Frame:From randomization to documented lymphoma progression or death from any cause, whichever occurs first, assessed up to 5 years
Safety Issue:
Description:Will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome.
Measure:Progression-free survival (PFS) (Phase I)
Time Frame:From entry onto study until lymphoma progression or death from any cause, assessed up to 3 years
Safety Issue:
Description:PFS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

September 13, 2017