Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 14 December 2015
• Main ID: NCT00538187
• Date of registration: 01/10/2007
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma
• Scientific title: Phase I Study of GX15-070 (NSC # 729280) and Bortezomib in Aggressive Relapsed/Recurrent Non-Hodgkin's Lymphoma
• Date of first enrolment: December 2007
• Target sample size: 18
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00538187
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Joseph Tuscano
• Affiliation: City of Hope Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically or cytologically confirmed relapsed or refractory non-Hodgkin lymphoma
for which standard curative or palliative measures do not exist or are no longer
effective, including any of the following subtypes:

- Follicular grade I, II, or III lymphoma

- Marginal zone lymphoma

- Mantle cell lymphoma

- Diffuse large B cell lymphoma

- Small lymphocytic lymphoma

- Must have had at least one prior chemotherapeutic regimen:

- Steroids or rituximab alone or local radiotherapy do not count as regimens

- Tositumomab or ibritumomab tiuxetan allowed as regimens

- Clear evidence of disease progression or lack of response after the most recent
therapy, including rituximab or local radiotherapy, is required

- At least 3 months since prior autologous stem cell transplantation and relapsed (>= 1
year since prior allogeneic transplantation and relapsed) and no active related
infections (i.e., fungal or viral)

- In the case of allogeneic transplantation relapse, there should be no active acute
graft-versus-host disease (GVHD) of any grade and no chronic GVHD other than mild
skin, oral, or ocular GVHD not requiring systemic immunosuppression

- No known active brain metastases, other neurological disorders/dysfunction or history
of seizure disorder, or other neurological dysfunction

- Karnofsky performance status 60-100%

- Life expectancy > 3 months

- Total bilirubin normal

- AST and ALT =< 2.5 times upper limit of normal

- Creatinine normal or creatinine clearance >= 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-barrier contraception during and for 3
months after the last dose of obatoclax mesylate

- At least 4 weeks since prior radiotherapy

- More than 2 days since prior steroids

- More than 2 weeks since prior low-dose chlorambucil

- WBC >= 3,000/mm^3

- ANC >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- At least 2 weeks since prior valproic acid

Exclusion Criteria:

- Uncontrolled concurrent medical condition or illness including, but not limited to,
any of the following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia including QTc > 450 msec

- Patients who are intolerant or refractory to prior treatment with bortezomib
(refractory is defined as no response to prior treatment with bortezomib)

- Chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)

- Rituximab within the past 3 months (unless there is evidence of progression)

- Patients who have not recovered from adverse events due to agents administered more
than 4 weeks earlier

- Other concurrent investigational agents

- Combination antiretroviral therapy for HIV-positive patients

- No history of allergic reactions attributed to bortezomib, polyethylene glycol (PEG
300), or polysorbate 20

- No psychiatric illness or social situation that would limit compliance with study
requirements



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Recurrent Grade 1 Follicular Lymphoma

Recurrent Grade 2 Follicular Lymphoma

Adult Non-Hodgkin Lymphoma

Recurrent Marginal Zone Lymphoma

Recurrent Adult Diffuse Large Cell Lymphoma

Recurrent Small Lymphocytic Lymphoma

Recurrent Grade 3 Follicular Lymphoma

Recurrent Mantle Cell Lymphoma

Intervention(s)

Other: laboratory biomarker analysis

Drug: bortezomib

Drug: obatoclax mesylate

Other: pharmacological study

Primary Outcome(s)

Maximum tolerated dose of obatoclax mesylate when administered with bortezomib [Time Frame: 35 days]

Secondary Outcome(s)

Toxicity as assessed by NCI CTCAE version 3.0 [Time Frame: Up to 26 weeks after completion of study treatment]

Pharmacokinetics of obatoclax mesylate when administered with bortezomib [Time Frame: Dose 1 of course 1, pre-infusion, 1 and 2 hours into the infusion, immediately prior to the end of the infusion, then at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, and 168 hours]

Secondary ID(s)

CDR0000566357

PHI-58

U01CA062505

NCI-2009-00253

Source(s) of Monetary Support

Please refer to primary and secondary sponsors