Clinical trial NCT01799083: Lower Dose Decitabine Based Therapy in Patients With Refractory and/or Chemotherapy Resistant Solid Tumors or B Cell Lymphomas
Official title: Phase 1/2 Study of Decitabine Alone and/or in Combination With Chemotherapy and/or Cytokine Induced Killer Cell Transfusion in Patients With Relapsed or Refractory Solid Tumors and B Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
B Cell Lymphoma
Keywords: Advanced solid tumors
B cell lymphoma
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2013-02-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Determine alone or in combination with chemotherapy or autologous cytokine induced killer cells are effective and safe in the treatment of patients with relapsed and/or refractory solid tumors or B Cell lymphomas.

Detailed description: The purpose of this study is to determine whether lower dose decitabine based therapy is safe and can effectively control tumor progression.

Eligibility criteria: Inclusion Criteria:

* Solid Tumor

  * Histologically confirmed advanced solid tumor
  * 1 to 3 prior treatment regimens
  * At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional computerized tomography (CT) scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per RECIST criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Medical Monitor
* B Cell Lymphoma

  * Histologically or cytologically confirmed B Cell Lymphoma.
  * Patients must have had an initial diagnosis of B Cell NHL (including follicular, small lymphocytic, lymphoplasmacytoid, and marginal zone lymphoma), indolent disease that transformed to a more aggressive subtype, as previously described or patients may have mantle cell lymphoma.
  * Patients are required to have received prior chemotherapy (alone or combined with rituximab or other treatment) and are considered refractory to (defined as no response, or progression within 6 months of completing therapy) or intolerant of continued rituximab or other treatment.
  * Patients may have received up to a maximum of four prior unique chemotherapy regimens, including if not contra-indicated autologous stem-cell transplantation (ASCT).
  * For patients to enroll in the expanded dose group for lymphoma, patients must have measurable disease

Exclusion Criteria:

* Disease Related

  * Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy, within 3 weeks prior to first dose or 6 weeks for antibody therapy
  * Radiation therapy or immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required); localized radiation therapy within 1 week prior to first dose
  * Subjects with prior brain metastases are permitted, but must have completed treatment and have no evidence of active central nervous system (CNS) disease for at least 4 weeks prior to first dose
  * For lymphoma patients; patients with prior stem cell transplant therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe GVHD.
  * Participation in an investigational therapeutic study within 3 weeks prior to first dose
  * Prior treatment with decitabine

Concurrent Conditions

* Major surgery within 3 weeks prior to first dose
* Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 3 months prior to first dose
* Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose
* Known or suspected HIV infection or subjects who are HIV seropositive
* Active hepatitis A, B, or C infection
* Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose

Ethical / Other

* Female subjects who are pregnant or lactating
* Any clinically significant psychiatric or medical condition that in the opinion of the Investigator could interfere with protocol adherence or a subject's ability to give informed consent

Primary outcomes:
measure: Response confirmed by non-investigational CT or MRI, or confirmed by biopsy
timeFrame: within the first 30 days after four-cycle treatment
Secondary outcomes:
measure: tumor marker
timeFrame: at least once within 30 days afther completing four-cycle treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Biotherapeutic Department of Chinese PLA General Hospital
state: Beijing
Study officials:
References:
citation: Lu XC, Yang B, Yu RL, Chi XH, Tuo S, Tuo CW, Zhu HL, Wang Y, Jiang CG, Fu XB, Yang Y, Liu Y, Yao SQ, Dai HR, Cai L, Li BJ, Han WD. Clinical study of autologous cytokine-induced killer cells for the treatment of elderly patients with diffuse large B-cell lymphoma. Cell Biochem Biophys. 2012 Jan;62(1):257-65. doi: 10.1007/s12013-011-9273-6.
citation: Yang B, Lu XC, Yu RL, Chi XH, Liu Y, Wang Y, Dai HR, Zhu HL, Cai LL, Han WD. Repeated transfusions of autologous cytokine-induced killer cells for treatment of haematological malignancies in elderly patients: a pilot clinical trial. Hematol Oncol. 2012 Sep;30(3):115-22. doi: 10.1002/hon.1012. Epub 2011 Aug 23.
citation: Fan H, Lu X, Wang X, Liu Y, Guo B, Zhang Y, Zhang W, Nie J, Feng K, Chen M, Zhang Y, Wang Y, Shi F, Fu X, Zhu H, Han W. Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report. J Immunol Res. 2014;2014:371087. doi: 10.1155/2014/371087. Epub 2014 May 21.
citation: Zhang Y, Wang J, Wang Y, Lu XC, Fan H, Liu Y, Zhang Y, Feng KC, Zhang WY, Chen MX, Fu X, Han WD. Autologous CIK cell immunotherapy in patients with renal cell carcinoma after radical nephrectomy. Clin Dev Immunol. 2013;2013:195691. doi: 10.1155/2013/195691. Epub 2013 Dec 9.