Hodgkin LymphomaPhase 2NCT00543582
MGCD0103 Administered in Combination With Azacitidine (Vidaza®) to Subjects With Relapsed or Refractory Hodgkin or Non-Hodgkin Lymphoma
A Phase 2 study testing MGCD0103 and Azacitidine in people with Hodgkin Lymphoma and Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma), run by Mirati Therapeutics Inc. at 4 sites in United States.
Trial summary
The first part of the study is to evaluate and determine if three different forms of MGCD0103 (free base FB-MGCD0103, tartaric acid free base [TA-FB-MGCD0103], and dihydrobromide [2HBr] salt formulation MGCD0103) have the same properties when given to patients with cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma)
- What is being tested?
- MGCD0103 and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2007to Mar 2009
- Phase
- Phase 2
- 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
Who may be able to join
- Age ≥ 18 years.
- Histologically confirmed diagnosis of classical Hodgkin's lymphoma or NHL (follicular, DLBCL, or mantle cell) and confirmed relapsed or refractory disease. 1)Subjects with a diagnosis of classical Hodgkin's lymphoma MUST have relapsed following a prior autologous, allogeneic or reduced intensity allogeneic stem cell transplant. Subjects who received an allogeneic transplant must have no evidence of graft versus host disease (GVHD), and have discontinued treatment with immunosuppressive agents ≥ 3 months prior to enrollment in this study. 2)Subjects with DLBCL must be ineligible for, or have refused, autologous stem cell transplant, or have relapsed following transplant. 3)Subjects with MCL must have relapsed after prior treatment and not be eligible for autologous stem cell transplant (ASCT) or have relapsed following ASCT. 4)Subjects with NHL who may have received a prior allogeneic stem cell transplant must have no evidence of GVHD, and have discontinued treatment with immunosuppressive agents ≥ 3 months prior to enrollment in this study.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Evidence of measurable disease (ie, at least one lesion that can accurately be measured in at least two dimensions as ≥15 mm with spiral CT scan). 1)If only single target lesion must be PET positive, and measure ≥20mm in two dimensions (required only for subjects with Hodgkin's lymphoma and DLBCL).
- Adequate organ function including: 1)Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (≥1500/mm^3); and 2)Platelets ≥ 50 x 10^9/L (≥50,000/mm^3); and 3)Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless increased due to Gilbert's Syndrome or hemolysis); and 4)AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; and 5)Serum creatinine ≤ 1.5 x ULN.
- At least 3 weeks elapsed since any prior anticancer therapy (standard or investigational) and full recovery (NCI CTCAE grade 1) from the toxic effects of that treatment.
- For women of childbearing potential, a negative serum pregnancy test within 7 days of treatment, a negative urine pregnancy test immediately prior to the first treatment with study drugs, and use of 2 physician-approved methods of birth control throughout the study and for a period of 3 months following the study.
- Written informed consent, willingness, and ability to comply with all study procedures.
Who cannot join
- Prior HDAC inhibitor and azacitidine combination therapy.
- Known hypersensitivity to azacitidine, HDAC inhibitors, and/or any components of MGCD0103, FB-MGCD0103, or TA-FB-MGCD0103 capsules and or azacitidine formulation components.
- Any condition that will put the subject at undue risk or discomfort as a result of adherence to study procedures (eg, requirement to take MGCD0103 with Gatorade®).
- Previous or concurrent malignancy except adequately treated basal cell or squamous skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
- Presence of significant involvement of the liver by lymphoma and impaired synthetic function as indicated by hypoalbuminemia of < 1.0 x LLN.
- Active and uncontrolled clinically significant infection.
Show all 15Show fewer
- Known Hepatitis B surface antigen (HepB SAg) positive or Hepatitis C antibody positive.
- Known infection with human immunodeficiency virus (HIV).
- History of melena or hematemesis within the last 3 months.
- Known central nervous system metastases.
- Less than 4 weeks elapsed since any major surgery.
- Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of beginning Part 1 of the study.
- WOCBP and men whose partners are WOCBP must use two acceptable methods of contraception while enrolled in this study, and for a period of 3 months following study drug treatment. Subjects unwilling or unable to follow this guideline will be excluded.
- Concurrent chronic treatment with therapeutic doses of systemic steroids.
- Prior or active disease or conditions that, in the opinion of the investigator, may interfere with the procedures or evaluations to be conducted in the study. This includes, but is not limited to, uncontrolled intercurrent illnesses such as symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
St. Francis Cancer Research Foundation
Beech Grove, Indiana, 46107
University of Texas, MD Anderson
Houston, Texas, 77030
Nevada Cancer Institute
Las Vegas, Nevada, 89135
Weill Medical College of Cornell University
New York, New York
About this study
Official title: A Phase 2, Open-label Trial to Evaluate the Efficacy and Safety of MGCD0103 Administered in Combination With Azacitidine (Vidaza®) to Subjects With Relapsed or Refractory Hodgkin or Non-Hodgkin Lymphoma, and to Evaluate the Pharmacokinetics of Different Formulations of MGCD0103
The first part of the study is to evaluate and determine if three different forms of MGCD0103 (free base FB-MGCD0103, tartaric acid free base [TA-FB-MGCD0103], and dihydrobromide [2HBr] salt formulation MGCD0103) have the same properties when given to patients with cancer. The second part of the study is to determine whether MGCD0103 administered in combination with azacitidine is effective and safe in treating subjects with relapsed or refractory Hodgkin's lymphoma or non-Hodgkin's lymphoma (NHL) (follicular or diffuse large B-cell [DLBCL]).
Read the detailed description
MGCD0103 and FB-MGCD0103 belong to a class of drugs known as histone deacetylase inhibitors (also called HDAC inhibitors). Azacitidine belongs to a class of anti-cancer drugs known as DNA de-methylating agents. Azacitidine (Vidaza®) was approved by the Food and Drug Administration (FDA) in 2004 for the treatment of myelodysplastic syndromes (MDS).
The combination of MGCD0103 and azacitidine has been given to about 50 people with leukemia or MDS in other clinical studies. This is the first study where the combination will be tested in people with lymphoma. Specifically, the study is designed to understand the following:
- How long single doses of TA-FB-MGCD0103, FB-MGCD0103 and MGCD0103 stay in the body, OR
- How long different doses of TA-FB-MGCD0103 and FB-MGCD0103 stay in the body; and
- How long MGCD0103 stays in the body when given with azacitidine; and
- What effect MGCD0103 and azacitidine have on the body and the study subject's type of lymphoma; and
- If the genetic and chemical make-up of the study subject's blood and/or tumor play a role in how she/he responds or does not respond to MGCD0103 and azacitidine.
- Conditions
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma)
- Being tested
- MGCD0103 and Azacitidine
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MGCD0103 and AzacitidineDrug
Also called Vidaza®
In Part 1 of the study, up to 22 people to enroll will receive a single, oral dose (75 mg gelcap) of MGCD0103 and FB-MGCD0103 during their first 2 weeks in the study. Up to 22 additional people will receive a single dose of both MGCD0103 and TA-FB-MGCE0103. The next group of people to enroll will receive 2 different single doses (25, 50, 100 mg) of FB-MGCD0103 or TA-FB-MGCD0103 during their first 2 weeks in the study.
In Part 2 of the study, from Day 1-5 of each 28-day cycle, all subjects will receive a dose of azacitidine (75 mg/m2) either subcutaneously or through an intravenous device, and on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, a single, oral dose (85 mg) of MGCD0103 until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: MGCD0103 and Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary efficacy is measured by: 1) PET, CT & physical exam, 2) overall response rate (complete response=disease is gone, partial response=disease has improved). Study treatment continues as long as the cancer is stable & side effects are tolerable.
Measured: every other cycle of 28 days each
Secondary outcomes (1)
Duration of response defined as: 1)the time of first documented objective response (either complete response or partial response) until the subject's disease gets worse, 2)how long his/her disease is stable.
Measured: 28 days after the last study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionMar 2009
- Study completionMar 2009
Why it stopped: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hodgkin LymphomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gregory Reid, MSc, MBA, Study director, MethylGene Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00543582
- Sponsor's protocol ID
- 103 PH US 2007 CL002
- Status last verified
- Jun 2015
- First submitted
- 11 Oct 2007
- Last updated
- 1 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-label Trial to Evaluate the Efficacy and Safety of MGCD0103 Administered in Combination With Azacitidine (Vidaza®) to Subjects With Relapsed or Refractory Hodgkin or Non-Hodgkin Lymphoma, and to Evaluate the Pharmacokinetics of Different Formulations of MGCD0103
- ClinicalTrials.gov ID
- NCT00543582
- Acronym / sponsor ID
- 103 PH US 2007 CL002
- Conditions
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 15 Oct 2007 (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.
The first part of the study is to evaluate and determine if three different forms of MGCD0103 (free base FB-MGCD0103, tartaric acid free base [TA-FB-MGCD0103], and dihydrobromide [2HBr] salt formulation MGCD0103) have the same properties when given to patients with cancer. The second part of the study is to determine whether MGCD0103 administered in combination with azacitidine is effective and safe in treating subjects with relapsed or refractory Hodgkin's lymphoma or non-Hodgkin's lymphoma (NHL) (follicular or diffuse large B-cell [DLBCL]).
Detailed description
MGCD0103 and FB-MGCD0103 belong to a class of drugs known as histone deacetylase inhibitors (also called HDAC inhibitors). Azacitidine belongs to a class of anti-cancer drugs known as DNA de-methylating agents. Azacitidine (Vidaza®) was approved by the Food and Drug Administration (FDA) in 2004 for the treatment of myelodysplastic syndromes (MDS).
The combination of MGCD0103 and azacitidine has been given to about 50 people with leukemia or MDS in other clinical studies. This is the first study where the combination will be tested in people with lymphoma. Specifically, the study is designed to understand the following:
- How long single doses of TA-FB-MGCD0103, FB-MGCD0103 and MGCD0103 stay in the body, OR
- How long different doses of TA-FB-MGCD0103 and FB-MGCD0103 stay in the body; and
- How long MGCD0103 stays in the body when given with azacitidine; and
- What effect MGCD0103 and azacitidine have on the body and the study subject's type of lymphoma; and
- If the genetic and chemical make-up of the study subject's blood and/or tumor play a role in how she/he responds or does not respond to MGCD0103 and azacitidine.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: MGCD0103 and Azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years.
- Histologically confirmed diagnosis of classical Hodgkin's lymphoma or NHL (follicular, DLBCL, or mantle cell) and confirmed relapsed or refractory disease. 1)Subjects with a diagnosis of classical Hodgkin's lymphoma MUST have relapsed following a prior autologous, allogeneic or reduced intensity allogeneic stem cell transplant. Subjects who received an allogeneic transplant must have no evidence of graft versus host disease (GVHD), and have discontinued treatment with immunosuppressive agents ≥ 3 months prior to enrollment in this study. 2)Subjects with DLBCL must be ineligible for, or have refused, autologous stem cell transplant, or have relapsed following transplant. 3)Subjects with MCL must have relapsed after prior treatment and not be eligible for autologous stem cell transplant (ASCT) or have relapsed following ASCT. 4)Subjects with NHL who may have received a prior allogeneic stem cell transplant must have no evidence of GVHD, and have discontinued treatment with immunosuppressive agents ≥ 3 months prior to enrollment in this study.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Evidence of measurable disease (ie, at least one lesion that can accurately be measured in at least two dimensions as ≥15 mm with spiral CT scan). 1)If only single target lesion must be PET positive, and measure ≥20mm in two dimensions (required only for subjects with Hodgkin's lymphoma and DLBCL).
- Adequate organ function including: 1)Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (≥1500/mm^3); and 2)Platelets ≥ 50 x 10^9/L (≥50,000/mm^3); and 3)Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless increased due to Gilbert's Syndrome or hemolysis); and 4)AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; and 5)Serum creatinine ≤ 1.5 x ULN.
- At least 3 weeks elapsed since any prior anticancer therapy (standard or investigational) and full recovery (NCI CTCAE grade 1) from the toxic effects of that treatment.
Key exclusion criteria (15 listed)
- Prior HDAC inhibitor and azacitidine combination therapy.
- Known hypersensitivity to azacitidine, HDAC inhibitors, and/or any components of MGCD0103, FB-MGCD0103, or TA-FB-MGCD0103 capsules and or azacitidine formulation components.
- Any condition that will put the subject at undue risk or discomfort as a result of adherence to study procedures (eg, requirement to take MGCD0103 with Gatorade®).
- Previous or concurrent malignancy except adequately treated basal cell or squamous skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
- Presence of significant involvement of the liver by lymphoma and impaired synthetic function as indicated by hypoalbuminemia of < 1.0 x LLN.
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 |
|---|---|---|
| MGCD0103 and AzacitidineAlso: Vidaza®In Part 1 of the study, up to 22 people to enroll will receive a single, oral dose (75 mg gelcap) of MGCD0103 and FB-MGCD0103 during their first 2 weeks in the study. Up to 22 additional people will receive a single dose of both MGCD0103 and TA-FB-MGCE0103. The next group of people to enroll will receive 2 different single doses (25, 50, 100 mg) of FB-MGCD0103 or TA-FB-MGCD0103 during their first 2 weeks in the study. In Part 2 of the study, from Day 1-5 of each 28-day cycle, all subjects will receive a dose of azacitidine (75 mg/m2) either subcutaneously or through an intravenous device, and on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, a single, oral dose (85 mg) of MGCD0103 until progression or unacceptable toxicity develops. | Drug | 1 |
Primary outcome
Primary efficacy is measured by: 1) PET, CT & physical exam, 2) overall response rate (complete response=disease is gone, partial response=disease has improved). Study treatment continues as long as the cancer is stable & side effects are tolerable.
Time frame: every other cycle of 28 days each
1 secondary outcome
Duration of response defined as: 1)the time of first documented objective response (either complete response or partial response) until the subject's disease gets worse, 2)how long his/her disease is stable.
Time frame: 28 days after the last study drug
Results and safety
The study was stopped early (reason given: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2015.
Related trials for Hodgkin Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
Active, not recruitingObservational study
Multi-omics Profiling of Relapsed Extranodal Natural Killer (NK)/T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
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.
Gregory Reid, MSc, MBA study director
MethylGene Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MGCD0103 and Azacitidine in people with Hodgkin Lymphoma and Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma), run by Mirati Therapeutics Inc. at 4 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 7 inclusion and 15 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: stopped early, as of the sponsor's last update on 1 Jul 2015. 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 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 phase mean?
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?
The study was stopped early (reason given: Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.). Results are not available in the source record.
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?
Primary efficacy is measured by: 1) PET, CT & physical exam, 2) overall response rate (complete response=disease is gone, partial response=disease has improved). Study treatment continues as long as the cancer is stable & side effects are tolerable. (time frame: every other cycle of 28 days each). 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 1 Jul 2015.