Hodgkin Lymphoma, Lymphoid Malignancies, Lymphoma, Multiple Myeloma, Non-hodgkin Lymphoma
Conditions
Keywords
Lymphoid Malignancies, Multiple Myeloma, Lymphoma, Hodgkin Lymphoma, Non-hodgkin Lymphoma, Follicular Lymphoma, Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Burkitt Lymphoma, Waldenstrom Macroglobulinemia, Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma
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.
Interventions
DRUGPralatrexate
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.
DRUGRomidepsin
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.
Sponsors
Jennifer Amengual
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of the Combination of Pralatrexate and Romidepsin in Phase 1 | Up to 1.5 years | The MTD was defined as the dose level at which one-third or fewer patients experienced a dose limiting toxicity. The MTD is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found. |
| Overall Response Rate (ORR) of Subjects Who Received Combination of Pralatrexate and Romidepsin in Phase 2 | Up to 3 years | ORR was defined as the number of subjects in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time. A partial response is a decrease in the size of a tumor or in the amount of cancer in the body, and a complete response is the disappearance of all signs of cancer in the body. In a clinical trial, measuring the ORR is one way to see how well a new treatment works. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) of Subjects Who Received Combination of Pralatrexate and Romidepsin in Phase 1 | Up to 1.5 years | ORR was defined as the number of subjects in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time. A partial response is a decrease in the size of a tumor or in the amount of cancer in the body, and a complete response is the disappearance of all signs of cancer in the body. In a clinical trial, measuring the ORR is one way to see how well a new treatment works. |
| Overall Survival (OS) of Subjects in Phase 2 | Up to 3 years | OS was defined as the length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. In a clinical trial, measuring the OS is one way to see how well a new treatment works. |
| Progression Free Survival (PFS) of Subjects in Phase 2 | Up to 3 years | PFS was defined as the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the PFS is one way to see how well a new treatment works. |
| Progression Free Survival (PFS) of Subjects in Phase 1 | Up to 1.5 years | PFS is defined as the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the PFS is one way to see how well a new treatment works. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJennifer Amengual, MD
Columbia University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized > 18 years | 47 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 3 | 0 / 3 | 0 / 3 | 2 / 3 | 0 / 5 | 0 / 3 | 0 / 6 | 1 / 18 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 5 / 5 | 3 / 3 | 6 / 6 | 13 / 18 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 0 / 3 | 1 / 3 | 1 / 3 | 2 / 5 | 1 / 3 | 2 / 6 | 4 / 18 |
Outcome results
None listed