PDX+Romi: Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I: Schedule A Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle |
Drug: Pralatrexate
Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2
Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.
Other Names:
Drug: Romidepsin
Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.
Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.
Other Names:
|
| Experimental: Phase I: Schedule B Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle |
Drug: Pralatrexate
Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2
Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.
Other Names:
Drug: Romidepsin
Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.
Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.
Other Names:
|
| Experimental: Phase II 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 |
Drug: Pralatrexate
Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2
Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.
Other Names:
Drug: Romidepsin
Phase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.
Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 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
- Overall survival (OS) of patients with T-Cell Lymphoma on study [Up to 3 years]
For Phase II
- Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma [Up to 3 years]
For Phase II
- 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
- Duration of response (DOR) of the study population. [Up to 1.5 years]
For Phase I
Eligibility Criteria
Criteria
Inclusion Criteria:
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
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Inclusion Criteria for Multiple Myeloma patients specified in the protocol
Exclusion Criteria:
-
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
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Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs
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No other investigational agents are allowed
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Central nervous system metastases, including lymphomatous meningitis
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History of allergic reactions to Pralatrexate or Romidepsin
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Uncontrolled intercurrent illness
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Pregnant women
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Nursing women
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Current malignancy or history of a prior malignancy, as outlined in the protocol
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Patient known to be Human Immunodeficiency Virus (HIV)-positive
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Active Hepatitis A, Hepatitis B, or Hepatitis C infection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 2 | Columbia University Irving Medical Center | New York | New York | United States | 10019 |
Sponsors and Collaborators
- Jennifer Amengual
Investigators
- Principal Investigator: Jennifer Amengual, MD, Columbia University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AAAJ5656