Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
- Conditions
- Lymphoid MalignanciesMultiple MyelomaLymphomaHodgkin LymphomaNon-hodgkin Lymphoma
- Interventions
- Registration Number
- NCT01947140
- Lead Sponsor
- Jennifer Amengual
- Brief Summary
This is a study to test how safe the combination of the drugs Romidepsin and Pralatrexate are in patients with lymphoid malignancies and to determine the dose of the combination of drugs that is safest. If the combination is determined to be safe, the study will continue accrual patients with peripheral T-Cell lymphoma (PTCL).
- Detailed Description
The non- Hodgkin lymphomas (NHL) represent a heterogeneous group of malignancies. Under the rubric of lymphoma exist some of the fastest growing cancers known to science, (Burkett's lymphoma, lymphoblastic lymphoma/leukemia), as well as some of the most indolent (small lymphocytic lymphoma, follicular lymphoma, and marginal zone lymphoma). This remarkable diversity of biology imposes significant challenges. Researchers are seeking to understand the cell of origin and differentiate what are sometimes subtle differences between the related sub-types of disease; and to identify the best treatments for these subtypes, with the ever-increasing likelihood that new understanding of the molecular pathogenesis of these diseases will result in an increase in new drugs for specific target populations.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
Phase I: Patients must have histologically confirmed relapsed or refractory Non-Hodgkin's lymphoma, Hodgkin's Disease or multiple myeloma (defined by World Health Organization (WHO) criteria).
Phase II: Patients must have histologically confirmed relapsed or refractory T-Cell Lymphoma (as defined by WHO criteria).
- Must have received first line chemotherapy. No upper limit for the number of prior therapies
- Evaluable Disease
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Patients must have adequate organ and marrow function as defined in the protocol
- Adequate Contraception
- Ability to understand and the willingness to sign a written informed consent document
- Inclusion Criteria for Multiple Myeloma patients specified in the protocol
-
Prior Therapy
- Exposure to chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
- Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs
- No other investigational agents are allowed
-
Central nervous system metastases, including lymphomatous meningitis
-
History of allergic reactions to Pralatrexate or Romidepsin
-
Uncontrolled intercurrent illness
-
Pregnant women
-
Nursing women
-
Current malignancy or history of a prior malignancy, as outlined in the protocol
-
Patient known to be Human Immunodeficiency Virus (HIV)-positive
-
Active Hepatitis A, Hepatitis B, or Hepatitis C infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase I: Schedule A Pralatrexate Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle Phase I: Schedule A Romidepsin Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle Phase I: Schedule B Pralatrexate Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle Phase II Pralatrexate Subjects will receive Pralatrexate 25 mg/m2 and Romidepsin 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle Phase I: Schedule B Romidepsin Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle Phase II Romidepsin Subjects will receive Pralatrexate 25 mg/m2 and Romidepsin 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin Up to 1.5 years For Phase I
Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma Up to 3 years For Phase II
- Secondary Outcome Measures
Name Time Method Maximum number of cycles received Up to 1.5 years For Phase II
Number of dose delays at the MTD Up to 1.5 years For Phase I
Overall survival (OS) of patients with T-Cell Lymphoma on study Up to 3 years For Phase II
Overall response rate (ORR) of the study population Up to 1.5 years For Phase I
Duration of response (DOR) of the combination in patients with T-Cell Lymphoma Up to 3 years For Phase II
Duration of response (DOR) of the study population. Up to 1.5 years For Phase I
Number of dose reductions at the MTD Up to 1.5 years For Phase I
Progression free survival (PFS) of the study population Up to 1.5 years For Phase I
Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma Up to 3 years For Phase II
Trial Locations
- Locations (3)
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States