B-cell Lymphoma, Hodgkin's Lymphoma, Peripheral T-cell Lymphoma, Relapsed or Refractory Lymphoproliferative Malignancies, Waldenstrom's Macroglobulinemia
Conditions
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
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.
Interventions
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.
DRUGGemcitabine Hydrochloride
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.
DIETARY_SUPPLEMENTVitamin B12
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.
DIETARY_SUPPLEMENTFolic Acid
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.
Sponsors
Acrotech Biopharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Responses Assessed by International Workshop Criteria (IWC) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) |
| 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 | 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). |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled between May 2007 and July 2010 across 16 study sites, all in the United States.
Pre-assignment details
12 patients were enrolled but not treated. Of these, 9 patients had events after enrollment that rendered them ineligible; 2 patients had progressive disease (PD); 1 patient withdrew consent. Since they were never dosed, these 12 patients were not included in efficacy or safety assessments.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 - Group A Phase 1 Treatment Group A had pralatrexate and gemcitabine administered on sequential days every week for 3 weeks followed by 1 week of rest (a 4 week cycle). The starting dose was 15 mg/m2 of pralatrexate and 400 mg/m2 of gemcitabine. | 7 |
| Phase 1 - Group B Phase 1 Treatment Group B had pralatrexate followed the next day by gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine. The starting dose was 10 mg/m2 of pralatrexate and 300 mg/m2 of gemcitabine. | 10 |
| Phase 1 - Group C Phase 1 Treatment Group C had pralatrexate followed 1 hour later by gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine. The starting dose was 10 mg/m2 of pralatrexate and 300 mg/m2 of gemcitabine. | 18 |
| Phase 2 - Group B Phase 2 Treatment Group B had 10 mg/m2 of pralatrexate followed the next day by 400 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine. | 38 |
| Phase 2 - Group C Phase 2 Treatment Group C had 15 mg/m2 of pralatrexate followed 1 hour later by 600 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine. | 34 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Progressive Disease - pt withdrew | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1 - Group A | Phase 1 - Group B | Phase 1 - Group C | Total | Phase 2 - Group B | Phase 2 - Group C |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants | 36 Participants | 14 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 7 Participants | 10 Participants | 71 Participants | 24 Participants | 28 Participants |
| Age, Continuous | 67.6 years STANDARD_DEVIATION 15 | 52.4 years STANDARD_DEVIATION 18 | 57.4 years STANDARD_DEVIATION 17 | 56.4 years STANDARD_DEVIATION 16.1 | 57.9 years STANDARD_DEVIATION 16 | 53.2 years STANDARD_DEVIATION 15 |
| Region of Enrollment United States | 7 participants | 10 participants | 18 participants | 107 participants | 38 participants | 34 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 42 Participants | 17 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 14 Participants | 65 Participants | 21 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 35 | 38 / 38 | 34 / 34 |
| serious Total, serious adverse events | 18 / 35 | 13 / 38 | 16 / 34 |
Outcome results
Primary
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.
Time frame: Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I
Population: All patients who completed at least 1 cycle of treatment were included in the efficacy analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 | Objective Responses Assessed by International Workshop Criteria (IWC) | 8 participants |
| Phase 2 - Group B | Objective Responses Assessed by International Workshop Criteria (IWC) | 5 participants |
| Phase 2 - Group C | Objective Responses Assessed by International Workshop Criteria (IWC) | 7 participants |
Secondary
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)
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 | Duration of Response | 174 days |
| Phase 2 - Group B | Duration of Response | 210 days |
| Phase 2 - Group C | Duration of Response | 170 days |
Secondary
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).
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 | Progression-free Survival (PFS) Time | 53.0 days |
| Phase 2 - Group B | Progression-free Survival (PFS) Time | 59.0 days |
| Phase 2 - Group C | Progression-free Survival (PFS) Time | 54.0 days |