Lenalidomide (Revlimid®) as Second Line Therapy in Patients With Chronic Graft-Vs-Host Disease (GVHD)
Condition: Graft-versus-Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Lenalidomide
Intervention description: 10 mg (capsule) by mouth on days 1-21 of a 28-day cycle, for a total of 6 cycles.
Intervention MeSH terms: Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Graft-versus-Host Disease; cGVHD; GVHD; Lenalidomide; Revlimid; CC-5013; Stem Cell Transplant; Allogeneic hematopoietic stem cell transplantation; Allogeneic HSCT; HSCT; Post-Transplant Prophylactic Immunosuppressive Therapy; Steroids; Standard-of-care steroid treatment; Corticosteroids; Prednisone; Medrol

Summary:

      The goal of this clinical research study is to learn if Revlimid® (lenalidomide), along with
      standard-of-care steroid treatment you are already receiving, can help to control Chronic
      Graft-Versus-Host Disease (cGVHD). The safety of this study drug in combination with the
      steroids will also be studied.

      Primary Objectives:

        -  To assess the response rate of chronic GVHD to Lenalidomide after failing steroids

        -  To evaluate the safety and tolerability of Lenalidomide in patients with chronic GVHD

      Secondary Objectives:

        -  To assess the steroid-sparing capacity of Lenalidomide (as proportion of patients able
           to discontinue steroids while receiving or following therapy with Lenalidomide)

        -  To assess changes in QOL after treatment with Lenalidomide

        -  To analyze survival at 6 and 12 months after initiation of Lenalidomide

        -  To evaluate relapse of underlying malignancy as well as second malignancies at 6 and 12
           months after initiation of Lenalidomide
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with chronic GVHD following allogeneic HSCT of any source (bone marrow,
             peripheral blood or cord blood stem cells), from any donor type (related, unrelated,
             mismatched) and with any type of malignancy.

          2. Patients must have failed a trial of steroids and calcineurin inhibitors. Steroids
             must have been given at an initial dose of 1 mg/kg/d of methylprednisolone (MP) or
             equivalent in combination with tacrolimus or cyclosporine. Steroid refractoriness or
             resistance will be defined as: 1- Lack of any response after 1 month of treatment with
             MP, including 15 days of at least 0.5 mg/kg/d, 2- Worsening of existing GVHD or new
             organ involvement at any time following one week of initiation of MP at 1 mg/kg/day,
             3- Reflare or worsening of GVHD at any time during steroid taper.

          3. Patients may have received steroids and calcineurin inhibitors (i.e. cyclosporine or
             tacrolimus) for chronic GVHD. Patients who have previously been treated for chronic
             GVHD with any other drug or treatment may be enrolled, provided the other drug or
             treatment was completed >/= 30 days before registration for study entry.

          4. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.

          5. White Blood Count (WBC) >/= 2,500/mm^3, Absolute neutrophil count (ANC)>/= 1,000/mm^3,
             platelet count >/= 50,000/mm^3

          6. Left ventricular ejection fraction >/= 40%. No uncontrolled arrythmias or symptomatic
             heart disease. forced expiratory volume at one second (FEV1), forced vital capacity
             (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) >/= 40%.

          7. Serum creatinine <2.0 mg/dL. Serum bilirubin <3 * upper limit of normal (ULN),
             aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transminase (SGOT) and
             Alanine transaminase (ALT)/ serum glutamic pyruvic transaminase (SGPT) < or = 5 * ULN.
             No evidence of chronic active hepatitis or cirrhosis.

          8. No uncontrolled infections.

          9. No evidence of malignancy (patients must be in complete remission from their
             malignancy)

         10. Patients must be able to provide written informed consent, and be 18 years or older at
             the time of signing consent.

         11. Patient must be able to return to clinic for follow up at least every 2 weeks for the
             first 2 months and at least monthly thereafter.

         12. Women of childbearing potential must have a negative serum or urine pregnancy test
             with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to therapy and repeated
             within 24 hours of starting study drug and must either commit to continued abstinence
             from heterosexual intercourse or agree to use 2 contraceptive methods. These birth
             control methods must be used for at least 4 weeks before, during and after
             lenalidomide therapy. Men must agree not to father a child and agrees to use a condom
             if his partner is of child bearing potential.

         13. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. (patients
             intolerant to ASA may use low molecular weight heparin).

        Exclusion Criteria:

          1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          2. Pregnant or lactating females.

          3. Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          4. Use of any other experimental drug or therapy within 28 days of baseline.

          5. Known hypersensitivity to thalidomide.

          6. The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs.

          7. Any prior use of Lenalidomide.

          8. Use of prior immunosuppressants other than steroids and calcineurin inhibitors (i.e.
             cyclosporine or tacrolimus).

          9. Known positive for HIV or infectious hepatitis, type A, B or C