Phase II Study of Oral Panobinostat in Adult Participants With Relapsed/Refractory Classical Hodgkin's Lymphoma
Condition: Classical Hodgkin's Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: Panobinostat
Intervention description: Panobinostat hard gelatin capsules.
Intervention MeSH terms: Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Classical Hodgkin Lymphoma; Classical Hodgkin's Lymphoma; Hodgkin Lymphoma; Hodgkin's Lymphoma; Nodular sclerosing; Mixed-cellularity; Lymphocyte-rich; Lymphocyte depleted; HL; Classical HL; Refractory Hodgkin's Lymphoma; Refractory Hodgkin Lymphoma; Refractory HL

Summary:

      This study evaluated the efficacy of oral panobinostat in participants with
      refractory/relapsed classical Hodgkins lymphoma (HL) who have received prior treatment with
      high dose chemotherapy and autologous stem cell transplant. Safety of panobinostat also was
      assessed. Other markers that may correlate with efficacy or safety were explored.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participant age is ≥ 18 years.

          2. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤
             2.

          3. Participant has a history of classical Hodgkin's Lymphoma (HL) (i.e. Nodular
             sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte depleted).

          4. Participant has progressive disease after receiving high dose chemotherapy with
             autologous hematopoietic stem cell transplant (AHSCT).

             Note: If last therapy was ≥ 18 months ago, then biopsy should be performed to confirm
             diagnosis.

             Note: Participant should have received ≤ 5 prior systemic treatment regimens (See
             Post-text supplement 2 for definitions and examples).

             Note: Participant will be allowed on study who have also received an allogeneic
             hematopoietic stem cell transplant, however this therapy alone is not sufficient for
             inclusion into this study.

          5. Participant has at least one site of measurable nodal disease at baseline ≥ 2.0
             centimeter (cm) in the longest transverse diameter and clearly measurable in at least
             two perpendicular dimensions, as determined by computed tomography (CT) scan (magnetic
             resonance imaging [MRI] is allowed only if CT scan can not be performed).

             Note: Participant with bone marrow involvement are eligible, but this criteria alone
             should not be used for disease measurement.

          6. Participant has the following laboratory values (labs may be repeated, if needed, to
             obtain acceptable values before screen fail):

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/liter (L) [International System of
                  Units {SI} units 1.5 x 10^9/L].

               -  Platelet count ≥ 75 x 10^9/L.

               -  Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for
                  serum albumin) or ionized calcium within normal limits (WNL) for the institution.

             Note: Potassium, calcium, magnesium, sodium, and/or phosphorus supplements may be
             given to correct values that are < lower limits of normal (LLN). Post-correction
             values must not be deemed to be a clinically significant abnormality prior to
             participant being dosed.

               -  Serum creatinine ≤ 1.5 x upper limits of normal (ULN).

               -  Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if participant has Gilbert
                  syndrome).

               -  Aspartate transaminase (AST)/ serum glutamic oxaloacetic transaminase (SGOT)
                  and/or alanine transaminase (ALT)/ serum glutamic pyruvic transaminase (SGPT) ≤
                  2.5 x ULN or ≤ 5.0 x ULN if the transaminase elevation is due to disease
                  involvement.

          7. Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone
             supplements to treat underlying hypothyroidism.

          8. Written informed consent was obtained from the participant prior to any study-specific
             screening procedures.

          9. Participant has the ability to swallow capsules or tablets.

        Exclusion Criteria:

          1. Participant has a history of prior treatment with a deacetylase (DAC) inhibitor
             including panobinostat.

          2. Participant will need valproic acid for any medical condition during the study or
             within 5 days prior to the first panobinostat treatment.

          3. Participant has been treated with monoclonal antibody therapy (e.g., rituximab or anti
             CD-30 antibody, etc.) within 4 weeks of start of study treatment.

          4. Participant has received chemotherapy or any investigational drug or undergone major
             surgery ≤ 2 weeks prior to starting study drug or whose side effects of such therapy
             have not resolved to ≤ grade 1.

          5. Participant has been treated with > 5 prior systemic lines of treatment (see Post-text
             supplement 2 for definitions and examples).

          6. Participant has received prior radiation therapy ≤ 4 weeks or limited field
             radiotherapy ≤ 2 weeks prior to start of study treatment or whose side effects of such
             therapy have not resolved to ≤ grade 1.

          7. Participant is using any anti-cancer therapy concomitantly.

          8. Participant treated with allogeneic hematopoietic stem cell transplant who is
             currently on or has received immunosuppressive therapy within 90 days prior to start
             of screening and/or have ≥ Grade 2 graft versus host disease (GvHD).

          9. Participant has a history of another primary malignancy ≤ 3 years before study entry,
             with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine
             cervix.

         10. Participant has a history of central nervous system (CNS) involvement with lymphoma.

         11. Participant has impaired cardiac function including any of the following:

               -  Complete left bundle branch block or use of a permanent cardiac pacemaker,
                  congenital long QT syndrome, history or presence of ventricular tachyarrhythmias,
                  clinically significant resting bradycardia (<50 beats per minute [bpm]), QT
                  interval (QTcF) > 450 milliseconds (msec) on screening electrocardiography (ECG),
                  or right bundle branch block + left anterior hemiblock (bifascicular block).

               -  Presence of atrial fibrillation (ventricular heart rate >100 bpm).

               -  Previous history angina pectoris or acute myocardial infarction (MI) within 6
                  months.

               -  Congestive heart failure (New York Heart Association functional classification
                  III-IV) or baseline multigated acquisition (MUGA)/Echo shows left ventricular
                  ejection fraction (LVEF) < 45%.

         12. Participant has any other clinically significant heart disease (e.g., uncontrolled
             hypertension).

         13. Participant has an impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of panobinostat (e.g., ulcerative disease,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or
             stomach and/or small bowel resection).

         14. Participant has unresolved diarrhea ≥ grade 2.

         15. Participant has any other concurrent severe and/or uncontrolled medical condition(s)
             (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection, chronic
             obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from
             any cause) that could cause unacceptable safety risks or compromise compliance with
             the protocol.

         16. Participant has a known history of human immunodeficiency virus (HIV) seropositivity
             (screening HIV testing is not required).

         17. Participant is using medications that have a relative risk of prolonging the QT
             interval or of inducing Torsade de Pointes, where such treatment cannot be
             discontinued or switched to a different medication prior to starting study drug.

         18. Participant is a woman who is pregnant or breast feeding, or a women of childbearing
             potential (WOCBP) not willing to use a double method of contraception during the study
             through 3 months after the end of treatment. One of these methods of contraception
             must be a barrier method. WOCBP are defined as sexually mature women who have not
             undergone a hysterectomy or who have not been naturally postmenopausal for at least 12
             consecutive months (i.e., who has had menses any time in the preceding 12 consecutive
             months). WOCBP must have a negative serum pregnancy test at baseline.

         19. Male participant whose sexual partner(s) are WOCBP who are not willing to use a double
             method of contraception, one of which includes a condom, during the study and for 3
             months after the end of treatment.

             Participants with any of the following contraindications to positron emission
             tomography (PET) are excluded from the [18F]- fludeoxyglucose (FDG) PET study (only
             applicable for centers participating in the PET study):

         20. Fasting blood glucose above 200 milligrams per deciliter (mg/dL), at time of PET scan.

         21. Inability to lay down for 60 minutes or has a history of claustrophobia.

         22. Participant not at a participating center.