Clinical trial NCT01947140: Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
Official title: Phase I/IIA Study of the Novel Antifolate Agent Pralatrexate in Combination With the Histone Deacetylase Inhibitor Romidepsin for the Treatment of Patients With Peripheral T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoid Malignancies
Multiple Myeloma
Lymphoma
Hodgkin Lymphoma
Non-hodgkin Lymphoma
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
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2013-09-20
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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
* 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin
timeFrame: Up to 1.5 years
measure: Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma
timeFrame: Up to 3 years
Secondary outcomes:
measure: Maximum number of cycles received
timeFrame: Up to 1.5 years
measure: Number of dose delays at the MTD
timeFrame: Up to 1.5 years
measure: Overall response rate (ORR) of the study population
timeFrame: Up to 1.5 years
measure: Duration of response (DOR) of the combination in patients with T-Cell Lymphoma
timeFrame: Up to 3 years
measure: Overall survival (OS) of patients with T-Cell Lymphoma on study
timeFrame: Up to 3 years
measure: Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma
timeFrame: Up to 3 years
measure: Number of dose reductions at the MTD
timeFrame: Up to 1.5 years
measure: Progression free survival (PFS) of the study population
timeFrame: Up to 1.5 years
measure: Duration of response (DOR) of the study population.
timeFrame: Up to 1.5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Columbia University
name: Jennifer Amengual, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amengual JE, Lichtenstein R, Lue J, Sawas A, Deng C, Lichtenstein E, Khan K, Atkins L, Rada A, Kim HA, Chiuzan C, Kalac M, Marchi E, Falchi L, Francescone MA, Schwartz L, Cremers S, O'Connor OA. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood. 2018 Jan 25;131(4):397-407. doi: 10.1182/blood-2017-09-806737. Epub 2017 Nov 15.