Clinical Trials /

Lenalidomide and Ipilimumab After Stem Cell Transplant in Treating Patients With Hematologic or Lymphoid Malignancies

NCT01919619

Description:

This pilot clinical trial studies the side effects of lenalidomide and ipilimumab after stem cell transplant in treating patients with hematologic or lymphoid malignancies. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide with ipilimumab may be a better treatment for hematologic or lymphoid malignancies.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lenalidomide and Ipilimumab After Stem Cell Transplant in Treating Patients With Hematologic or Lymphoid Malignancies
  • Official Title: A Pilot Study of Lenalidomide Alternating With Ipilimumab Post Allogeneic and Autologous Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: 2012-0947
  • SECONDARY ID: NCI-2013-02213
  • SECONDARY ID: 2012.0947
  • SECONDARY ID: 2012-0947
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01919619

Conditions

  • B-Cell Non-Hodgkin Lymphoma
  • Hematopoietic and Lymphoid Cell Neoplasm
  • Leukemia
  • Lymphoma
  • Plasma Cell Myeloma
  • T-Cell Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyTreatment (lenalidomide and ipilimumab)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidTreatment (lenalidomide and ipilimumab)

Purpose

This pilot clinical trial studies the side effects of lenalidomide and ipilimumab after stem cell transplant in treating patients with hematologic or lymphoid malignancies. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide with ipilimumab may be a better treatment for hematologic or lymphoid malignancies.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the safety of lenalidomide in combination with ipilimumab in autologous and
      allogeneic stem cell transplantation.

      SECONDARY OBJECTIVES:

      I. Overall response rate. II. Overall survival, progression-free survival. III. Cumulative
      incidence of acute and chronic graft-versus-host disease (GVHD) with the competing risk of
      relapse in allogeneic transplant patients.

      OUTLINE:

      Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21 of courses 1, 3, 5 and
      7. Beginning 1-3 days after the last dose of lenalidomide patients receive one dose of
      ipilimumab intravenously (IV) over 90 minutes of courses 2, 4, 6 and 8. Treatment repeats
      every 28 days for up to 8 courses in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up at 1, 3, 6, 12, 24, and 36
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (lenalidomide and ipilimumab)ExperimentalPatients receive lenalidomide PO QD on days 1-21 of courses 1, 3, 5 and 7. Beginning 1-3 days after the last dose of lenalidomide patients receive one dose of ipilimumab IV over 90 minutes of courses 2, 4, 6 and 8. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
  • Ipilimumab
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Hematologic or lymphoid malignancy

          -  Autologous patients can be included anytime within 6 months post-transplant, if they
             had no signs of progression and meet one of the following criteria: i. leukemia; ii.
             lymphoma (all types of B and T cell lymphoma); iii. multiple myeloma

          -  Allogeneic patients if: i. patients had engrafted donor cells (i.e., > 20% donor
             T-cell from peripheral blood [PB]/polymerase chain reaction [PCR]); and, ii. patients
             NOT in complete remission (CR) after their allogeneic transplant, and off tacrolimus
             and/or mycophenolate mofetil for at least 3 to 4 weeks with no signs of GVHD; or, iii.
             patients had evidence of relapse after their transplant who are off tacrolimus and/or
             mycophenolate mofetil or other immunosuppressants for GVHD for 3 to 4 weeks with no
             signs of GVHD (prednisone doses =< 10 mg are permitted as stated previously)

          -  No active infection

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Platelets > 75 x 10^9/L

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Performance status: Eastern Cooperative Oncology Group (ECOG) 2 or less or Karnofsky
             of at least 60

          -  Cardiac ejection fraction (EF) >= 45% by 2-dimensional echocardiogram (2D-ECHO) within
             3 months of study entry (or within 1 month if received chemotherapy within the past 3
             months)

          -  Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and
             diffusing capacity of the lung for carbon monoxide (DLCO) >= 40% within 3 months of
             study entry (or within 1 month if received chemotherapy within the past 3 months)

          -  Serum creatinine =< 1.6 mg/dL and creatinine clearance >= 30 ml/min; creatinine
             clearance will be calculated using the Cockcroft-Gault equation

          -  Serum glutamate pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase
             (SGOT) less than 2 x the upper limit of normal range (unless related to Gilbert's
             disease or medications)

          -  Direct bilirubin < 1.6 (unless related to Gilbert's disease or medications)

          -  Patient or legally authorized representative able to sign informed consent

          -  Females of childbearing potential (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 study entry

        Exclusion Criteria:

          -  Immunotherapy or chemotherapy with approved or investigational anticancer therapeutics
             within 4 weeks of first dose

          -  Patients on alemtuzumab within 6 weeks prior to consenting

          -  Active congestive heart failure (New York Heart Association [NYHA] class III to IV),
             symptomatic ischemia or conduction abnormalities uncontrolled by conventional
             interventions; myocardial infarction within 6 months of study entry

          -  Deep vein thrombosis or pulmonary embolism within 3 months of study entry

          -  Pregnant or breast-feeding females; (lactating females must agree not to breast-feed
             while taking lenalidomide)

          -  Acute active infection requiring intravenous antibiotics, antiviral (except antiviral
             directed at hepatitis B), or antifungal agents within 14 days of first dose

          -  Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or
             hepatitis B (except for patients with hepatitis B surface antigen [Sag] or core
             antibody receiving and responding to antiviral therapy directed at hepatitis B: these
             patients are allowed)

          -  Patients with other known malignancies within the past three years except: i.
             adequately treated basal or squamous cell skin cancer; ii. carcinoma in situ of the
             cervix; iii. prostate cancer with Gleason score < 6 with stable prostate-specific
             antigen (PSA) over the past three months; iv. breast cancer in situ with full surgical
             resection

          -  Significant neuropathy (grades 3 to 4 or grade 2 pain)

          -  Known hypersensitivity to thalidomide, lenalidomide or ipilimumab

          -  Active life-threatening autoimmune disease

          -  Active GVHD or recent GVHD and still on > 10 mg prednisone (or equivalent)

          -  Prior auto-immune disease
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity rate
Time Frame:Up to 30 days following the last dose of study drugs
Safety Issue:
Description:Graded according to the National Cancer Institute Common Toxicity Criteria. The toxicity rate will be estimated in each arm along with a corresponding 95% credible interval. Toxicity will also be summarized by arm, type, and grade.

Secondary Outcome Measures

Measure:Response rate
Time Frame:112 days
Safety Issue:
Description:The response rate at the end of four cycles will be estimated with a 95% confidence interval.
Measure:Overall response rate
Time Frame:Up to 36 months
Safety Issue:
Description:The overall response rate will be estimated with a 95% confidence interval.
Measure:Overall survival
Time Frame:Up to 36 months
Safety Issue:
Description:Kaplan-Meier survival curves will be used to estimate overall survival. Cox proportional hazards regression analysis will be used to model the association between overall survival and disease and demographic covariates of interest, including data from the correlative cytokine, immune, and pharmacokinetic studies.
Measure:Progression-free survival
Time Frame:Up to 36 months
Safety Issue:
Description:Kaplan-Meier survival curves will be used to estimate progression-free survival. Cox proportional hazards regression analysis will be used to model the association between overall survival and disease and demographic covariates of interest, including data from the correlative cytokine, immune, and pharmacokinetic studies.
Measure:Cumulative incidence of acute graft-versus-host disease
Time Frame:Up to 30 days following the last dose of study drugs
Safety Issue:
Description:The method of Gooley et al will be used to estimate the cumulative incidence of acute graft-versus-host disease with the competing risk of relapse in allogeneic transplant patients.
Measure:Cumulative incidence of chronic graft-versus-host disease
Time Frame:Up to 36 months
Safety Issue:
Description:The method of Gooley et al will be used to estimate the cumulative incidence of chronic graft-versus-host disease with the competing risk of relapse in allogeneic transplant patients.
Measure:Incidence of other organ toxicity
Time Frame:Up to 36 months
Safety Issue:
Description:Graded according to the National Cancer Institute Common Toxicity Criteria.
Measure:Incidence of secondary immune-based disease
Time Frame:Up to 36 months
Safety Issue:
Description:Secondary immune-based diseases include arthritis, lupus, and thyroid dysfunction.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

December 2, 2019