Study of Pralatrexate & Gemcitabine With B12 & Folic Acid to Treat Relapsed/Refractory Lymphoproliferative Malignancies

NCT00481871 | Completed Phase 1 Results

• 1 other identifier: PDX-009
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 15

Brief Summary

This study is for patients with lymphoproliferative malignancies that have progressed after receiving a previous treatment (relapsed) or are no longer responding to treatment (refractory). To be in this study, patients must have certain types of Hodgkin's lymphoma (HL), peripheral T-cell lymphoma (PTCL), or B-cell lymphoma, including Waldenstrom's macroglobulinemia. This study is being done to find doses of the combination of pralatrexate and gemcitabine with vitamin B12 and folic acid that can be safely given to patients with these types of lymphoma and explore the effectiveness of the treatment.

Conditions

Relapsed or Refractory Lymphoproliferative Malignancies; Hodgkin's Lymphoma; Peripheral T-cell Lymphoma; B-cell Lymphoma; Waldenstrom's Macroglobulinemia

Keywords

Lymphoproliferative malignancies; Lymphoma; Hodgkin's lymphoma (HL); Non-Hodgkin's lymphoma (NHL); PTCL; T/NK-cell leukemia/lymphoma; T-cell lymphoma/leukemia (HTLV 1+); Angioimmunoblastic T-cell lymphoma; Blastic NK lymphoma; Anaplastic large cell lymphoma; T/NK-cell lymphoma; Enteropathy-type intestinal lymphoma; Hepatosplenic T-cell lymphoma; Extranodal peripheral T/NK-cell lymphoma; Subcutaneous panniculitis T-cell lymphoma; Transformed mycosis fungoides; PDX; Pralatrexate; Gemcitabine; Gemzar; Vitamin B12; Folic acid

Outcome Measures

Primary Outcomes (1)

• Objective Responses Assessed by International Workshop Criteria (IWC)

  Number of participants who achieved an objective response. Objective response was defined as a tumor response assessment of either complete response (CR) or partial response (PR) and was determined only for patients with measurable disease at baseline. A tumor response assessment reported by IWC without PET was used for any analyses in cases where an IWC+PET evaluation was not done.

  Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I

Secondary Outcomes (2)

• Duration of Response

  Response assessments were performed no less than every 3 cycles in the Phase 1 part of the study and every 8 weeks (± 1 week) in the Phase 2a part of the study

• Progression-free Survival (PFS) Time

  Response assessments were performed no less than every 3 cycles in the Phase 1 part of the study and every 8 weeks (± 1 week) in the Phase 2a part of the study

Study Arms (2)

Pralatrexate & Gemcitabine - Sequential Days

EXPERIMENTAL

Drug: Pralatrexate Injection; Drug: Gemcitabine Hydrochloride; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid

Pralatrexate & Gemcitabine - Same Day

EXPERIMENTAL

Drug: Pralatrexate Injection; Drug: Gemcitabine Hydrochloride; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid

Interventions

Pralatrexate Injection DRUG

Intravenous (IV) push administration over 30 seconds to 5 minutes into a patent IV line containing normal saline (0.9% sodium chloride). Sequential Dosing: 10 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met. Same Day Dosing: 15 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met.

Also known as: FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin

Pralatrexate & Gemcitabine - Same Day; Pralatrexate & Gemcitabine - Sequential Days

Gemcitabine Hydrochloride DRUG

Gemcitabine will be prepared and administered as an IV infusion as per manufacturer instructions. Sequential Dosing: 400 mg/m2 every 2 weeks (days 2 and 16) of a 4-week cycle until criteria for discontinuation per the protocol are met. Same Day Dosing: 600 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met.

Also known as: Gemcitabine, Gemzar®, Eli Lilly and Company, Gemcitabine Hydrochloride (HCl) for Injection

Pralatrexate & Gemcitabine - Same Day; Pralatrexate & Gemcitabine - Sequential Days

Vitamin B12 DIETARY_SUPPLEMENT

1 mg intramuscular injection Administered within 10 weeks of enrollment, every 8-10 weeks throughout the study and for at least 30 days after last dose of pralatrexate.

Also known as: Cyanocobalamin

Pralatrexate & Gemcitabine - Same Day; Pralatrexate & Gemcitabine - Sequential Days

Folic Acid DIETARY_SUPPLEMENT

1 mg orally Administered daily for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days after last dose of pralatrexate.

Also known as: Vitamin B9, Folate, Folacin

Pralatrexate & Gemcitabine - Same Day; Pralatrexate & Gemcitabine - Sequential Days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Progression of disease (PD) after at least 1 prior treatment (any number of prior therapies allowed). PD after last prior treatment and recovered from toxic effects of prior therapy. Patients treated with an FDA-approved monoclonal antibody therapy may be enrolled at any time after the therapy if they have PD.
• PTCL patients must have received single-agent pralatrexate as a prior therapy.
• Eastern Cooperative Oncology Group performance status ≤ 2.
• Adequate blood, liver and kidney function per laboratory tests.
• Has taken 1 mg daily oral folic acid for at least 7 days prior to planned start of pralatrexate and received 1 mg vitamin B12 intramuscularly within 10 weeks of the planned start of pralatrexate.
• Females of childbearing potential must practice a medically acceptable contraceptive regimen from first dose until at least 30 days after last dose of pralatrexate and have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Postmenopausal (defined as greater than 12 months since last menses) and surgically sterilized females do not require this test.
• Males who are not surgically sterile must practice a medically acceptable contraceptive regimen from first dose until at least 90 days after last dose of pralatrexate.
• Give written informed consent.
• Phase 1
• \. B-cell: lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia); plasma cell myeloma/plasmacytoma; hairy cell leukemia.
• Phase 2a
• PTCL: precursor T/Natural Killer (NK) neoplasms, with the exception of blastic NK lymphoma; T-cell prolymphocytic leukemia; T-cell large granular lymphocytic leukemia; mycosis fungoides (MF), except transformed MF; Sézary syndrome; primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis.
• B-cell: plasma cell myeloma/plasmacytoma; hairy cell leukemia.
• Relapsed HL or diffuse large B-cell lymphoma patients who are candidates for high dose therapy and autologous stem cell transplantation (SCT) and for whom it is a standard curative option.
• Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, must be disease free for at least 5 years.

Sponsors & Collaborators

• Acrotech Biopharma Inc.: lead

Study Sites (15)

University of California at Los Angeles

Los Angeles, California, 90095-7077, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115-6013, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

The Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

New York University Hospital

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10017, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Therapy & Research Center

San Antonio, Texas, 78229-4427, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Recurrence; Hodgkin Disease; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell; Waldenstrom Macroglobulinemia; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Leukemia; Immunoblastic Lymphadenopathy; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Extranodal NK-T-Cell

Interventions

10-propargyl-10-deazaaminopterin; Gemcitabine; Commerce; WW Domain-Containing Oxidoreductase; Vitamin B 12; Folic Acid

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Technology, Industry, and Agriculture; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring

Results Point of Contact

• Title: Michael Saunders, MD
• Organization: Allos Therapeutics, Inc.

msaunders@allos.com

303-426-6262

Study Officials

• Michael Saunders, MD

  Spectrum Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2007
• First Posted: June 4, 2007
• Study Start: May 1, 2007
• Primary Completion: May 1, 2011
• Study Completion: August 1, 2011
• Last Updated: January 7, 2020
• Results First Posted: September 18, 2012

Record last verified: 2019-12

Locations

US (15)