Relapsed or Refractory Lymphoproliferative MalignanciesPhase 1/2NCT00481871
Study of Pralatrexate & Gemcitabine With B12 & Folic Acid to Treat Relapsed/Refractory Lymphoproliferative Malignancies
A Phase 1/2 study testing Pralatrexate Injection, Gemcitabine Hydrochloride and Vitamin B12 in people with Relapsed or Refractory Lymphoproliferative Malignancies and Hodgkin's Lymphoma, run by Acrotech Biopharma Inc. at 15 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Lymphoproliferative Malignancies, Hodgkin's Lymphoma, Peripheral T-cell Lymphoma
- What is being tested?
- Pralatrexate Injection, Gemcitabine Hydrochloride and Vitamin B12
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 15 sitesUnited States
- Study dates
- May 2007to Aug 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase 1: Histologically/cytologically confirmed lymphoproliferative malignancy. Patients with Hodgkin lymphoma (HL) or non-HL are eligible, with exceptions per exclusion criteria.
- Phase 2a: Histologically/cytologically confirmed HL, peripheral T-cell lymphoma (PTCL), or B-cell lymphoma including Waldenström's macroglobulinemia, with exceptions per exclusion criteria.
- 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.
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- 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.
Who cannot join
- Phase 1
- 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.
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- 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.
- Congestive heart failure Class III/IV.
- Uncontrolled hypertension.
- Human immunodeficiency virus (HIV)- positive diagnosis with CD4 less than 100 or detectable viral load within past 3 months and receiving anti-retroviral therapy.
- Hepatitis B or C virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
- Central nervous system disease.
- Undergone an allogeneic SCT.
- Patients with disease refractory to peripheral blood SCT, or who have relapsed less than 100 days since an autologous or peripheral blood SCT.
- Active uncontrolled infection, underlying medical condition including unstable heart disease, or other serious illness impairing the ability to receive protocol treatment.
- Major surgery within 2 weeks of planned start of treatment.
- Receipt of any conventional chemotherapy or radiation therapy (encompassing greater than 10% of bone marrow) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the study.
- Receipt of systemic corticosteroids within 7 days of study treatment, unless on a continuous dose of no more than 10 mg/day of prednisone for at least 1 month.
- Use of investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the study.
- Received a monoclonal antibody within 3 months without evidence of PD.
- Previous exposure to pralatrexate and/or gemcitabine if discontinued due to treatment-related toxicity.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115-6013
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Chicago Hospital
Chicago, Illinois, 60637
Rocky Mountain Cancer Center
Denver, Colorado, 80218
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
UT MD Anderson Cancer Center
Houston, Texas, 77030
University of California at Los Angeles
Los Angeles, California, 90095-7077
New York University Hospital
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10017
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Cancer Therapy & Research Center
San Antonio, Texas, 78229-4427
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: A Phase 1/2a Open-label Study of Pralatrexate and Gemcitabine With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Lymphoproliferative Malignancies
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
- Being tested
- Pralatrexate Injection, Gemcitabine Hydrochloride, Vitamin B12, Folic Acid
- 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
- Medical subject headings
- Recurrence, Hodgkin Disease, Lymphoma, T-Cell, Peripheral, Lymphoma, B-Cell, Waldenstrom Macroglobulinemia, Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pralatrexate InjectionDrug
Also called FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin
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 called Gemcitabine, Gemzar®, Eli Lilly and Company, Gemcitabine Hydrochloride (HCl) for Injection
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.
Vitamin B12Dietary supplement
Also called Cyanocobalamin
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.
Folic AcidDietary supplement
Also called Vitamin B9, Folate, Folacin
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.
| Study group | Role | What they receive |
|---|---|---|
| Pralatrexate & Gemcitabine - Sequential Days | Experimental | Not described Receives: Drug: Pralatrexate Injection; Drug: Gemcitabine Hydrochloride; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid |
| Pralatrexate & Gemcitabine - Same Day | Experimental | Not described Receives: Drug: Pralatrexate Injection; Drug: Gemcitabine Hydrochloride; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Duration of response was defined as the number of days between the date of first tumor response assessment of objective response to the time of the first tumor response assessment of progressive disease (PD) or death due to any cause (date of first PD assessment or death - date of first objective response assessment + 1)
Measured: 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
PFS time was calculated as the number of days from study day 1 to the date of PD or death, regardless of cause (date of PD or death - study day 1 + 1).
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2007 (estimated)
- Study startMay 2007
- Primary completionMay 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed or Refractory Lymphoproliferative MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acrotech Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Saunders, MD, Study director, Spectrum Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00481871
- Sponsor's protocol ID
- PDX-009
- Status last verified
- Dec 2019
- First submitted
- 1 Jun 2007
- Last updated
- 7 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Open-label Study of Pralatrexate and Gemcitabine With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Lymphoproliferative Malignancies
- ClinicalTrials.gov ID
- NCT00481871
- Acronym / sponsor ID
- PDX-009
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Acrotech Biopharma Inc.Industry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- May 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 4 Jun 2007 (estimated)
- Results
- Posted 18 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Phase 1: Histologically/cytologically confirmed lymphoproliferative malignancy. Patients with Hodgkin lymphoma (HL) or non-HL are eligible, with exceptions per exclusion criteria.
- Phase 2a: Histologically/cytologically confirmed HL, peripheral T-cell lymphoma (PTCL), or B-cell lymphoma including Waldenström's macroglobulinemia, with exceptions per exclusion criteria.
- 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.
Key exclusion criteria (21 listed)
- Phase 1
- 1. B-cell: lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia); plasma cell myeloma/plasmacytoma; hairy cell leukemia.
- Phase 2a
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pralatrexate InjectionAlso: FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterinIntravenous (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. | Drug | Pralatrexate & Gemcitabine - Same Day, Pralatrexate & Gemcitabine - Sequential Days |
| Gemcitabine HydrochlorideAlso: Gemcitabine, Gemzar®, Eli Lilly and Company, Gemcitabine Hydrochloride (HCl) for InjectionGemcitabine 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. | Drug | Pralatrexate & Gemcitabine - Same Day, Pralatrexate & Gemcitabine - Sequential Days |
| Vitamin B12Also: Cyanocobalamin1 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. | Dietary supplement | Pralatrexate & Gemcitabine - Same Day, Pralatrexate & Gemcitabine - Sequential Days |
| Folic AcidAlso: Vitamin B9, Folate, Folacin1 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. | Dietary supplement | Pralatrexate & Gemcitabine - Same Day, Pralatrexate & Gemcitabine - Sequential Days |
Primary outcome
Objective Responses Assessed by International Workshop Criteria (IWC)
Time frame: Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I
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.
2 secondary outcomes
Duration of Response
Time frame: 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
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Saunders, MD study director
Spectrum Pharmaceuticals, Inc
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pralatrexate Injection, Gemcitabine Hydrochloride and Vitamin B12 in people with Relapsed or Refractory Lymphoproliferative Malignancies and Hodgkin's Lymphoma, run by Acrotech Biopharma Inc. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Responses Assessed by International Workshop Criteria (IWC) (time frame: Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2020.