LeukemiaPhase 1NCT01164709
Nelfinavir Mesylate and Bortezomib in Treating Patients With Relapsed or Progressive Advanced Hematologic Cancer
A Phase 1 study testing bortezomib and nelfinavir mesylate in people with Leukemia and Lymphoma, run by Swiss Cancer Institute at 4 sites in Switzerland.
Trial summary
RATIONALE: Nelfinavir mesylate and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of hematologic cancer by blocking blood flow to the cancer. Giving nelfinavir mesylate together with bortezomib may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphoma, Mature T-cell and Nk-cell Neoplasms
- What is being tested?
- bortezomib and nelfinavir mesylate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesSwitzerland
- Study dates
- Jul 2010to Nov 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
DISEASE CHARACTERISTICS:
- Diagnosed with advanced hematologic malignancies meeting the following criteria:
- Multiple myeloma
- Received ≥ 2 lines of prior chemotherapy (induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant with or without maintenance therapy is considered one line of therapy)
- Acute myeloid leukemia
- Acute lymphoblastic leukemia
- Diffuse large B-cell lymphoma
- Hodgkin lymphoma
- Mantle cell lymphoma
- Mature T- and NK-cell neoplasms restricted to the following WHO-defined entities:
- T-cell prolymphocytic leukemia
- T-cell large granular lymphocytic leukemia
- Aggressive NK-cell leukemia
- Adult T-cell leukemia/lymphoma
- Extranodal NK/T-cell lymphoma (nasal type)
- Mycosis fungoides
- Sézary syndrome
- Primary CD30-positive T-cell lymphoproliferative disorders
- Primary cutaneous anaplastic large cell lymphoma
- Primary cutaneous gamma-delta T-cell lymphoma
- Peripheral T-cell lymphoma (not otherwise specified)
- Angioimmunoblastic T-cell lymphoma
- Anaplastic large cell lymphoma (ALK-positive/ALK-negative)
- Grade 3B follicular lymphoma
- Relapsed following or progressed during standard therapy
- Meeting the following criteria:
- Standard intensive therapy is not feasible
- Current disease state for which there is no standard effective therapy
- Refused standard therapy where no curative option exists
- Measurable disease, defined as the following:
- Myeloma: measurable serum monoclonal protein > 1 g/dL for IgG, or > 0.5 g/dL for IgA, IgM or IgD, or difference between involved and uninvolved free light chain levels in serum > 100 mg/L
- Lymphoma: must have ≥ 1 lesion measurable by CT (longest diameter ≥ 15 mm)
- Acute leukemia: ≥ 20% blasts in bone marrow or in peripheral blood (≥ 200/mL blasts in peripheral blood)
- No HIV-associated lymphoma
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 75,000/mm³ (if bone marrow impairment, ≥ 20,000/mm^3)
- Hemoglobin > 80 g/L (if considered to be caused by the underlying hematologic malignancy or bone marrow impairment, > 80 g/L after transfusion)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) (if suspected hemolysis, direct bilirubin ≤ 1.5 times ULN)
- ALT ≤ 2.5 times ULN
- Calculated creatinine clearance > 30 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 12 months after completion of study treatment
- Willing and capable to comply with an oral regimen
- Capable of understanding information given by the investigator on the trial
- Able to adhere and remain in geographic proximity to allow proper staging, treatment, and followup
- No other non-hematologic malignancy within the past 5 years, except adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer
- No known chronic hepatitis B or C infection or known HIV infection
- No serious underlying medical condition (at the judgment of the investigator) which would impair the ability of the patient to participate in the trial, including any of the following:
- Active autoimmune disease
- Uncontrolled diabetes
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric disorder
- No myocardial infarction within the past 6 months
- No polyneuropathy > grade 1 significantly interfering with activities of daily living or painful polyneuropathy
- No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No more than 4 prior lines of chemotherapeutic regimens (induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant with or without maintenance therapy is considered one line of therapy)
- More than 30 days since prior treatment in a clinical trial
- More than 30 days since prior and no concurrent chemotherapy or biologic agents
- For patients with acute leukemia, hydroxyurea may be given up to 48 hours before first administration of the trial treatment, and low dose cytarabine (up to 20 mg/m^2) and mitoxantrone up to 20 mg up to 14 days before first dosing
- At least 1 week since prior and no concurrent CYP3A4 modulators
- No concurrent other experimental drugs
- No concurrent radiotherapy
- No concurrent antineoplastic therapy with chemotherapeutic or biologic agents
Trial locations and contacts
4 sites in 1 country.
Switzerland4 sites
Inselspital Bern
Bern, CH-3010
Kantonsspital Graubuenden
Chur, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
Kantonsspital - St. Gallen
Sankt Gallen, CH-9007
About this study
Official title: Phase I Trial of Nelfinavir and Bortezomib in Advanced Hematologic Malignancies
RATIONALE: Nelfinavir mesylate and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of hematologic cancer by blocking blood flow to the cancer. Giving nelfinavir mesylate together with bortezomib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of nelfinavir mesylate when given together with bortezomib in treating patients with relapsed or progressive advanced hematologic cancer.
Read the detailed description
OBJECTIVES:
- To assess the safety of nelfinavir mesylate in combination with bortezomib in patients with relapsed or progressive, advanced hematologic malignancies.
- To establish the phase II recommended dose of nelfinavir mesylate in these patients.
OUTLINE: This is a multicenter, dose-escalation study of nelfinavir mesylate.
Patients receive oral nelfinavir mesylate twice daily on days 1-21 and bortezomib IV on days 8, 11, 15, and 18 in course 1. Course 1 has a duration of 28 days. Beginning in course 2, patients receive oral nelfinavir mesylate twice daily on days 1-14 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for 2 courses. Patients with responding disease may continue to receive nelfinavir mesylate and bortezomib for up to 4 additional courses.
After completion of study treatment, patients are followed for 30 days.
- Conditions
- Leukemia, Lymphoma, Mature T-cell and Nk-cell Neoplasms, Multiple Myeloma and Plasma Cell Neoplasm
- Being tested
- bortezomib, nelfinavir mesylate
- Keywords
- refractory multiple myeloma, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult diffuse large cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent mantle cell lymphoma, recurrent adult T-cell leukemia/lymphoma, adult nasal type extranodal NK/T-cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, T-cell large granular lymphocyte leukemia, anaplastic large cell lymphoma, recurrent grade 3 follicular lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, aggressive NK-cell leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22)
- Medical subject headings
- Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Large B-Cell, Diffuse, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called Velcade
Bortezomib i.v., day 8, 11, 15, 18; 1.3 mg/m2
nelfinavir mesylateDrug
Also called Viracept
p.o., days 1 to 21; dose level: (625), 1250, 1875, or 2500 mg, 2x/d
| Study group | Role | What they receive |
|---|---|---|
| bortezomib + nelfinavir | Experimental | escalation 3 by 3 cohorts Receives: Drug: bortezomib; Drug: nelfinavir mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity
Measured: during first cycle
Secondary outcomes (2)
Objective response
Measured: during treatment
Adverse events according to NCI CTCAE v.4.0
Measured: during treatment + 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2010 (estimated)
- Study startJul 2010
- Primary completionJul 2012
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christoph Driessen, MD, Study chair, Cantonal Hospital of St. GallenDagmar Hess, MD, Principal investigator, Cantonal Hospital of St. GallenRoger von Moos, MD, Principal investigator, Kantonsspital GraubündenThomas Pabst, MD, Principal investigator, Insel Gruppe AG, University Hospital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01164709
- Sponsor's protocol ID
- SAKK 65/08
- Other IDs
- SWS-SAKK-65/08, EU-21051, SWS-SAKK-JC26866138LYM1005, CDR0000681442
- Status last verified
- May 2019
- First submitted
- 16 Jul 2010
- Last updated
- 15 May 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Driessen C, Kraus M, Joerger M, Rosing H, Bader J, Hitz F, Berset C, Xyrafas A, Hawle H, Berthod G, Overkleeft HS, Sessa C, Huitema A, Pabst T, von Moos R, Hess D, Mey UJ. Treatment with the HIV protease inhibitor nelfinavir triggers the unfolded protein response and may overcome proteasome inhibitor resistance of multiple myeloma in combination with bortezomib: a phase I trial (SAKK 65/08). Haematologica. 2016 Mar;101(3):346-55. doi: 10.3324/haematol.2015.135780. Epub 2015 Dec 11.
PubMed 26659919
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Nelfinavir and Bortezomib in Advanced Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01164709
- Acronym / sponsor ID
- SAKK 65/08
- Conditions
- Leukemia, Lymphoma, Mature T-cell and Nk-cell Neoplasms, Multiple Myeloma and Plasma Cell Neoplasm
- Keywords
- refractory multiple myeloma, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult diffuse large cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent mantle cell lymphoma, recurrent adult T-cell leukemia/lymphoma, adult nasal type extranodal NK/T-cell lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Swiss Cancer InstituteUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Jul 2012 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 19 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Nelfinavir mesylate and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of hematologic cancer by blocking blood flow to the cancer. Giving nelfinavir mesylate together with bortezomib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of nelfinavir mesylate when given together with bortezomib in treating patients with relapsed or progressive advanced hematologic cancer.
Detailed description
OBJECTIVES:
- To assess the safety of nelfinavir mesylate in combination with bortezomib in patients with relapsed or progressive, advanced hematologic malignancies.
- To establish the phase II recommended dose of nelfinavir mesylate in these patients.
OUTLINE: This is a multicenter, dose-escalation study of nelfinavir mesylate.
Patients receive oral nelfinavir mesylate twice daily on days 1-21 and bortezomib IV on days 8, 11, 15, and 18 in course 1. Course 1 has a duration of 28 days. Beginning in course 2, patients receive oral nelfinavir mesylate twice daily on days 1-14 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for 2 courses. Patients with responding disease may continue to receive nelfinavir mesylate and bortezomib for up to 4 additional courses.
After completion of study treatment, patients are followed for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bortezomib + nelfinavir | Experimental | Drug: bortezomib, Drug: nelfinavir mesylateescalation 3 by 3 cohorts |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| bortezomibAlso: VelcadeBortezomib i.v., day 8, 11, 15, 18; 1.3 mg/m2 | Drug | bortezomib + nelfinavir |
| nelfinavir mesylateAlso: Viraceptp.o., days 1 to 21; dose level: (625), 1250, 1875, or 2500 mg, 2x/d | Drug | bortezomib + nelfinavir |
Primary outcome
Dose limiting toxicity
Time frame: during first cycle
2 secondary outcomes
Objective response
Time frame: during treatment
Adverse events according to NCI CTCAE v.4.0
Time frame: during treatment + 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2019.
- Results publication: PubMed 26659919Driessen C, Kraus M, Joerger M, Rosing H, Bader J, Hitz F, Berset C, Xyrafas A, Hawle H, Berthod G, Overkleeft HS, Sessa C, Huitema A, Pabst T, von Moos R, Hess D, Mey UJ. Treatment with the HIV protease inhibitor nelfinavir triggers the unfolded protein response and may overcome proteasome inhibitor resistance of multiple myeloma in combination with bortezomib: a phase I trial (SAKK 65/08). Haematologica. 2016 Mar;101(3):346-55. doi: 10.3324/haematol.2015.135780. Epub 2015 Dec 11.
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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.
Christoph Driessen, MD study chair
Cantonal Hospital of St. Gallen
Dagmar Hess, MD principal investigator
Cantonal Hospital of St. Gallen
Roger von Moos, MD principal investigator
Kantonsspital Graubünden
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bortezomib and nelfinavir mesylate in people with Leukemia and Lymphoma, run by Swiss Cancer Institute at 4 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Switzerland. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Dose limiting toxicity (time frame: during first cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01164709, which also lists 1 linked publication.
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 15 May 2019.