MyelomaEarly Phase 1NCT01396200
Cyclophosphamide and Pulse Dexamethasone With Rapamycin or Hydroxychloroquine
A Early Phase 1 study testing Hydroxychloroquine and Rapamycin in people with Myeloma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
The purpose of this study is to determine the feasibility of giving (i) rapamycin or (ii) hydroxychloroquine (HCQ), with standard doses of infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/refractory multiple myeloma, as well as the feasibility of obtaining multiple blood and bone… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloma
- What is being tested?
- Hydroxychloroquine and Rapamycin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to Oct 2012
- Phase
- Early 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
Who may be able to join
- Each subject must meet ALL of the following criteria during screening to be enrolled:
- Histologically confirmed multiple myeloma
- Documented relapse or persistent disease after at least one prior therapy (which may include autologous and allogeneic bone marrow transplantation)
- Need for further therapy for myeloma, as determined by the patients treating physician
- Age 18 years
- ECOG PS 0-2
Who cannot join
- History of allergic reactions to compounds of similar chemical or biological composition to rapamycin or hydroxychloroquine
- Patients may not take any of the following medications while on study (in the rapamycin arms only), but will be considered eligible if medication is discontinued 72 hrs prior to first dose of Rapamycin:
- Carbamazepine (e.g. Tegretol)
- Rifabutin (e.g. Mycobutin)
- Rifampin (e.g. Rifadin)
- Rifapentine (e.g. Priftin)
Show all 44Show fewer
- St. Johns Wort Clarithromycin (e.g. Biaxin)
- Cyclosporin e.g. (Neorla or Sandimmune)
- Diltiazem (e.g. Cardizem)
- Erythromycin (e.g. Akne-Mycin, Ery-Tab)
- Itraconazole (e.g. Sporonox)
- Fluconazole (e.g. Diflucan)
- Ketoconazole (e.g. Nizoral)
- Telithromycin (e.g. Ketek)
- Verapamil (e.g. Calan SR, Isoptin, Verelan)
- Voriconazole (e.g. VFEND)Tacrolimus (e.g. Prograf)
- Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis (well-controlled psoriasis allowed provided under the care of a specialist who agrees to monitor the patient for exacerbations)
- Patients with the following cytopenias: ANC 1.0 x 109/L; Platelets 50 x 109/L
- Serum Creatinine 2.5 mg/dL; Total or Direct Bilirubin 2.0 mg/dL; Fasting Glucose 200mg/dL
- Other conditions that would require therapy with hydroxychloroquine, including but not limited to, any of the following:
- Systemic lupus
- Rheumatoid arthritis
- Porphyria cutanea tarda
- Malaria treatment or prophylaxis
- Other active malignancy, except:
- Basal cell or squamous cell carcinoma of the skin
- Treated carcinoma in situ
- Localized prostate adenocarcinoma (stage T1a or T1b) with a stable PSA for a period of at least 4 months allowed
- Patients with a prior malignancy treated with chemotherapy, biologic agents, and/or radiation are eligible for this study if they have completed therapy 4 years previously with no evidence of recurrent disease
- Patients with a prior malignancy treated with surgery alone are eligible for this study if they have completed therapy 2 years previously with no evidence of recurrent disease
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Uncontrolled ongoing infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Uncontrolled cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
- Inability to understand or unwillingness to sign the informed consent document
- Concurrent anti-myeloma therapy within:
- 7 days of prior corticosteroids
- 14 days of prior antimyeloma agents, including thalidomide or lenalidomide
- 28 days of a different investigational regimen
- 14 days of any radiation
- Women of child-bearing who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 30 days after the last dose of study drug.
- Women who are pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Pilot Study of Infusional Cyclophosphamide and Pulse Dexamethasone With Rapamycin or Hydroxychloroquine in Patients With Relapsed or Refractory Multiple Myeloma
The purpose of this study is to determine the feasibility of giving (i) rapamycin or (ii) hydroxychloroquine (HCQ), with standard doses of infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/refractory multiple myeloma, as well as the feasibility of obtaining multiple blood and bone marrow samples during treatment to assess the pharmacodynamic effects of the treatment.
Read the detailed description
Multiple myeloma is a plasma cell neoplasm with median survival of 3 to 5 years. Recent advances have improved patient outlook, but the disease remains incurable and patients become refractory to treatments, develop organ dysfunction from myeloma itself, and encounter severe toxicities from therapies, limiting further treatment options. Subjects over the age of 18 with relapsed or refractory multiple myeloma who have had at least one prior therapy, have a life expectancy of at least 4 weeks and an ECOG performance status of 0,1 or 2 will be included. The investigators propose an initial pilot trial to test the feasibility of giving standard chemotherapy with infusional cyclophosphamide and pulse dexamethasone (cy/dex) for four days, together with the investigational agents, oral rapamycin (cohort A), and in a separate parallel arm, oral hydroxychloroquine (HCQ) (cohort B). The investigators will enroll 3 patients on cohort A and 3 patients on cohort B, both at the planned 1st dose level for the overall phase I/II trial which will succeed this trial if feasibility is demonstrated. The 6 patients from this pilot trial will be included in total number of patients for the overall study which will be completed when further funding is secured. Feasibility will be defined by the ability to deliver the regimen as planned and the ability to perform the planned correlative studies. Subjects will receive up to 12 cycles and will be followed for 12 months after the last cycle. Data collected will include toxicity, response rates, correlative studies to examine the pharmacodynamics of mTOR inhibition and autophagy and the pharmacokinetics of rapamycin and HCQ.
- Conditions
- Myeloma
- Being tested
- Hydroxychloroquine, Rapamycin
- Medical subject headings
- Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose level 1: 800mg by mouth daily Dose level -1: 600 mg by mouth daily
RapamycinDrug
Dose level 1: Loading dose 12mg, daily dose 4mg Dose level -1: Loading dose 9mg,daily dose 3mg
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine (Cohort B) | Experimental | Infusional cyclophosphamide 300mg/m2/day for 4 days IV and dexamethasone 40mg/day orally or IV for 4 days on days 1 through 4. Hydroxychloroquine oral will be given on days 5 through 28 of cycle 1 and every day of all subsequent cycles (to be given with milk or food at approximately the same time each day) Receives: Drug: Hydroxychloroquine |
| Rapamycin (Cohort A) | Experimental | Infusional cyclophosphamide 300 mg/m2/day for 4 days IV and dexamethasone 40 mg/day orally or IV for 4 days on days 3 through 6. Rapamycin oral loading dose will be given on day 1 followed by an oral daily dose for an additional 5 days (days 2 through 6) to be given on an empty stomach at approximately the same time each day suggested 11 am)This dosing schedule is the same for all cycles. Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events
The feasibility of administering rapamycin and hydroxychloroquine (HCQ), with standard doses of infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/refractory multiple myeloma.
Secondary outcomes (1)
Toxicities and response to the regimen
To demonstrate the feasibility of performing the planned correlative studies to examine mTOR signaling and autophagy activiation and inhibition.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2011 (estimated)
- Study startJun 2011
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dan Vogl, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01396200
- Sponsor's protocol ID
- UPCC 09411
- Status last verified
- Feb 2013
- First submitted
- 14 Jul 2011
- Last updated
- 26 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Infusional Cyclophosphamide and Pulse Dexamethasone With Rapamycin or Hydroxychloroquine in Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01396200
- Acronym / sponsor ID
- UPCC 09411
- Conditions
- Myeloma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 18 Jul 2011 (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 purpose of this study is to determine the feasibility of giving (i) rapamycin or (ii) hydroxychloroquine (HCQ), with standard doses of infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/refractory multiple myeloma, as well as the feasibility of obtaining multiple blood and bone marrow samples during treatment to assess the pharmacodynamic effects of the treatment.
Detailed description
Multiple myeloma is a plasma cell neoplasm with median survival of 3 to 5 years. Recent advances have improved patient outlook, but the disease remains incurable and patients become refractory to treatments, develop organ dysfunction from myeloma itself, and encounter severe toxicities from therapies, limiting further treatment options. Subjects over the age of 18 with relapsed or refractory multiple myeloma who have had at least one prior therapy, have a life expectancy of at least 4 weeks and an ECOG performance status of 0,1 or 2 will be included. The investigators propose an initial pilot trial to test the feasibility of giving standard chemotherapy with infusional cyclophosphamide and pulse dexamethasone (cy/dex) for four days, together with the investigational agents, oral rapamycin (cohort A), and in a separate parallel arm, oral hydroxychloroquine (HCQ) (cohort B). The investigators will enroll 3 patients on cohort A and 3 patients on cohort B, both at the planned 1st dose level for the overall phase I/II trial which will succeed this trial if feasibility is demonstrated. The 6 patients from this pilot trial will be included in total number of patients for the overall study which will be completed when further funding is secured. Feasibility will be defined by the ability to deliver the regimen as planned and the ability to perform the planned correlative studies. Subjects will receive up to 12 cycles and will be followed for 12 months after the last cycle. Data collected will include toxicity, response rates, correlative studies to examine the pharmacodynamics of mTOR inhibition and autophagy and the pharmacokinetics of rapamycin and HCQ.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine (Cohort B) | Experimental | Drug: HydroxychloroquineInfusional cyclophosphamide 300mg/m2/day for 4 days IV and dexamethasone 40mg/day orally or IV for 4 days on days 1 through 4. Hydroxychloroquine oral will be given on days 5 through 28 of cycle 1 and every day of all subsequent cycles (to be given with milk or food at approximately the same time each day) |
| Rapamycin (Cohort A) | Experimental | Drug: RapamycinInfusional cyclophosphamide 300 mg/m2/day for 4 days IV and dexamethasone 40 mg/day orally or IV for 4 days on days 3 through 6. Rapamycin oral loading dose will be given on day 1 followed by an oral daily dose for an additional 5 days (days 2 through 6) to be given on an empty stomach at approximately the same time each day suggested 11 am)This dosing schedule is the same for all cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed multiple myeloma
- Documented relapse or persistent disease after at least one prior therapy (which may include autologous and allogeneic bone marrow transplantation)
- Need for further therapy for myeloma, as determined by the patients treating physician
- Age 18 years
- ECOG PS 0-2
Key exclusion criteria (44 listed)
- History of allergic reactions to compounds of similar chemical or biological composition to rapamycin or hydroxychloroquine
- Patients may not take any of the following medications while on study (in the rapamycin arms only), but will be considered eligible if medication is discontinued 72 hrs prior to first dose of Rapamycin:
- Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis (well-controlled psoriasis allowed provided under the care of a specialist who agrees to monitor the patient for exacerbations)
- Patients with the following cytopenias: ANC 1.0 x 109/L; Platelets 50 x 109/L
- Serum Creatinine 2.5 mg/dL; Total or Direct Bilirubin 2.0 mg/dL; Fasting Glucose 200mg/dL
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 |
|---|---|---|
| HydroxychloroquineDose level 1: 800mg by mouth daily Dose level -1: 600 mg by mouth daily | Drug | Hydroxychloroquine (Cohort B) |
| RapamycinDose level 1: Loading dose 12mg, daily dose 4mg Dose level -1: Loading dose 9mg,daily dose 3mg | Drug | Rapamycin (Cohort A) |
Primary outcome
Number of Participants with Adverse Events
The feasibility of administering rapamycin and hydroxychloroquine (HCQ), with standard doses of infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/refractory multiple myeloma.
1 secondary outcome
Toxicities and response to the regimen
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 26 Feb 2013.
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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.
Dan Vogl, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Hydroxychloroquine and Rapamycin in people with Myeloma, run by Abramson Cancer Center at Penn Medicine at 1 site 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 6 inclusion and 44 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 26 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Number of Participants with Adverse Events. 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 26 Feb 2013.