AzTrials
AzTrials

Lymphoid Malignancies (New or Relapsed)Early Phase 1NCT01184885

A Pilot Study to Determine the Safety and Tolerability of Sirolimus Given With Hyper-CVAD Chemotherapy

A Early Phase 1 study testing Hyper-CVAD and Sirolimus in people with Lymphoid Malignancies (New or Relapsed) and Acute Lymphoblastic Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a pilot study, assessing the feasibility, safety and toxicity of an mTOR (mammalian target of Rapamycin) inhibitor (MTI), rapamycin, when administered with HyperCVAD (Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicine and Dexamethasone), with an ultimate goal to perform a phase II study to evaluate… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hyper-CVAD and Sirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
2 sitesUnited States
Study dates
Jul 2010to Apr 2013
Phase
Early Phase 1
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

  • Patients must have a diagnosis of one of the following lymphoid malignancies (new or relapsed):
  • Acute Lymphoblastic Leukemia (B and T cell, Philadelphia Chromosome Negative)
  • Burkitt Lymphoma
  • Burkitt - type Lymphoma
  • Lymphoblastic Lymphoma
  • Mantle Cell Lymphoma
Show all 16Show fewer
  • Adult T cell Leukemia/ lymphoma
  • Patients must be >18 years old
  • Patients must have an ECOG performance status of 0 or 1(see attachment 1).
  • Patients must have a life expectancy of at least 4 weeks.
  • Patients must be able to consume oral medication.
  • Patients must have completed any radiotherapy four weeks prior to study entry, 0-2 weeks for local palliative XRT (small port).
  • Patients must have recovered from the toxic effects of any prior chemotherapy to < grade 2 (except alopecia).
  • Required initial laboratory values: Creatinine < or = 2.0mg/dL; total or direct bilirubin < or = 1.5mg/dL (if not due to the leukemia or lymphoma itself); SGPT(ALT) < or = 3xULN; glucose <200 mg/dL, negative pregnancy test for women with child-bearing potential.
  • Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
  • Patients may have had a prior stem cell transplant (autologous or allogeneic), however they may not have active GvHD, nor be on any immunosuppression

Who cannot join

  • Patients must not be receiving any chemotherapy agents (except Hydroxyurea)
  • Intrathecal ARA-C and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system).
  • Patients must not be receiving growth factors, except for erythropoietin.
  • Patients with a current second malignancy requiring systemic therapy, other than non-melanoma skin cancers, are not eligible.
  • Patients with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible.
  • Patients taking any of the following drugs while on-study are not eligible:
Show all 27Show fewer
  • Carbamazepine (e.g. Tegretol)
  • Rifabutin (e.g. Mycobutin)
  • Rifampin (e.g. Rifadin)
  • Rifapentine (e.g. Priftin)
  • St. John's Wort- may decrease the effects of sirolimus by decreasing the amount of sirolimus in the body
  • Clarithromycin (e.g. Biaxin)
  • Cyclosporin e.g. (Neorla or Sandimmune)
  • Diltiazem (e.g. Cardizem)
  • Erythromycin (e.g. Akne-Mycin, Ery-Tab)
  • Itraconazole (e.g. Sporanox)
  • Ketoconazole (e.g. Nizoral)
  • Telithromycin (e.g. Ketek)
  • Verapamil (e.g. Calan SR, Isoptin, Verelan)
  • Voriconazole (e.g. VFEND) - May increase the effects of sirolimus by increasing the amount of this medicine in the body. [Cannot be taken within 72 hours prior to or subsequent to receiving rapamycin, but may be taken prior to or after the above time period]
  • Tacrolimus (e.g. Prograf) - May cause liver transplant rejection or serious side effects in patients on sirolimus.
  • Patients with known HIV positivity or AIDS-related illness are not eligible.
  • Patients with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible.
  • Patients must not have evidence of cerebellar dysfunction or prior history of cerebellar dysfunction with Ara-C administration.
  • Patients must not have received any investigational agents within 30 days of study entry.
  • Patients must not be pregnant or breastfeeding. Pregnancy tests must be obtained for all females of child-bearing potential. Pregnant or lactating patients are ineligible for this study due to the unknown human fetal or teratogenic toxicities of rapamycin. Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.
  • Patients who have uncontrolled infection are not eligible. Patients must have any active infections under control. Fungal disease must be stable for at least 2 weeks before study entry. Patients with bacteremia must have documented negative blood cultures prior to study entry.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Pilot Study of Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone (Hyper-CVAD) With Sirolimus for the Treatment of Adult Acute Lymphoblastic Leukemia and Aggressive Lymphoid Malignancies

This is a pilot study, assessing the feasibility, safety and toxicity of an mTOR (mammalian target of Rapamycin) inhibitor (MTI), rapamycin, when administered with HyperCVAD (Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicine and Dexamethasone), with an ultimate goal to perform a phase II study to evaluate response rates and survival in adults with Acute Lymphoblastic Leukemia (ALL) and aggressive lymphoid malignancies.

Read the detailed description

The primary objective of this trial is to characterize the feasibility, safety and tolerability of therapy with Hyper-CVAD and Rapamycin in adults with ALL and other aggressive lymphoid malignancies.

This study will evaluate the effectiveness of Rapamycin given in combination with Hyper-CVAD during A treatment cycles, and Methotrexate and Cytarabine in B treatment cycles. Both cycles will also contain the drug Rituximab if the patient has a B cell type of leukemia or lymphoma.

This combination of drugs are being studied to determine whether or not these drugs will have an effect in treating this disease.

Current therapeutic regimens for induction of remission in ALL are broadly similar. There is no single best regimen for induction therapy. The hyper-CVAD regimen is of particular interest because it does not include asparaginase as part of the therapeutic regimen and the results of induction are similar to other published regimens.

The HyperCVAD regimen with or without rituximab is also an accepted induction regimen for lymphoblastic lymphoma, Burkitt and Burkitt like lymphoma, Mantle Cell Lymphoma, and ALL in the elderly. The regimen has also been used as a salvage regimen in patients with the above diagnoses who have relapsed after another induction regimen.

This trial will add a novel agent, an mTOR inhibitor (MTI), rapamycin, to act synergistically with the HyperCVAD regimen. This is a pilot study, assessing the feasibility, safety and toxicity of this regimen, with an ultimate goal to perform a phase II study to evaluate response rates and survival.

This is a pilot study of the Hyper-CVAD regimen with Rapamycin for the treatment of adults with acute lymphoblastic leukemia or other aggressive lymphoid malignancies. The standard Hyper-CVAD regimen will be used, with the addition of the investigational agent, Rapamycin. Hyper-CVAD alone is one of the current standard induction and salvage regimens used to treat ALL and other aggressive lymphoid malignancies.

Subjects included will have either de novo, relapsed, or refractory ALL or another aggressive lymphoid malignancy.

Chemotherapy will consist of 4 'A' cycles alternating with 4 'B' cycles, every 21 days, or as count recovery allows (at least 14 days apart) as follows: 1A; 1B; 2A; 2B, 3A; 3B; 4A; 4B. This is dependent on white blood cell count recovery.

Being tested
Hyper-CVAD, Sirolimus
Keywords
hyperCVAD, rapamycin, lymphoid malignancies, lymphoblastic leukemia, B and T cell, philadelphia chromosome negative, burkitt lymphoma, burkitt-type lymphoma, lymphoblastic lymphoma, mantle cell lymphoma, adult t cell leukemia, adult t cell lymphoma
Medical subject headings
Recurrence, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Lymphoma, Mantle-Cell, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hyper-CVADDrug

    Also called Cytoxan, Endoxan, Neosar, Procytox

    • Cycle A: Cyclophosphamide 300mg/m2 every 12 hours on days 3-5; Vincristine 2mg/day on days 6 and 13; Doxorubicin 50mg/m2 on day 6; Decadron 40mg/ day po on days 3-6 and 13-16; Methotrexate 12mg IT on day 4; Ara-C 100mg IT on day 9.
    • Cycle B: Methotrexate 1000mg/m2 on day 3; Leucovorin 50mg every 6 hours starting 24 hours from the beginning of the MTX infusion until MTX levels are < 0.1 umol/L; Ara-C 3000mg/m2 every 12 hours on days 4 and 5; Methotrexate 12mg IT on day 4; Ara-C 100mg IT on day 9.
    • Rituximab (if given) will be 375 mg/m2 on Days 3 and 13 of Cycle A and on Days 4 and 9 of cycle B, for a total of 8 doses over the first 4 courses.

  • SirolimusDrug

    Also called Rapamycin

    Sirolimus loading dose of 12mg on day 1 followed by a single daily dose of 4 mg/ day on days 2 through 7 (Cycle A) and on days 2 through 6 (Cycle B)

Study groups in NCT01184885
Study groupRoleWhat they receive
Hyper-CVAD and SirolimusExperimentalHyper-CVAD and Sirolimus
Receives: Drug: Hyper-CVAD; Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Count Recovery That Allows for Starting a Phase II Study to Evaluate Response Rates and Survival

    This will be assessed by evaluating the tolerability of this regimen compared to historical controls who received Hyper-CVAD or Hyper-CVAD/ Rituximab regimens. The treatment will be designated feasible for an individual subject if in 80% of chemotherapy cycles the subject has count recovery that allows for starting the subsequent cycle by Day 28. Count recovery is defined as ANC (absolute neutrophil count) of > 0.5 x 10^9/L and platelet count > 50 x 10^9/L.

    Hyper-CVAD/Rapamycin will be deemed acceptable if it is feasible to administer in 80% or more of subjects.

    Measured: 18 months

Secondary outcomes (2)

  1. Induction Mortality

    Induction mortality. Hyper-CVAD/ Rapamycin will be considered acceptable if induction mortality does not exceed 31% in patients older than 60, or 15% in those younger than 60

    Measured: 18 months

  2. Complete Response

    To describe response rates to hyper-CVAD and sirolimus in adults with ALL and other aggressive lymphoid malignancies.

    Bone marrow (<5% blasts) with adequate bone marrow cellularity, no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts except for platelets (neutrophil count =1,000/µL).

    Measured: Every 21 days or as count recovery allows (at least 14 days apart) up to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionMar 2011
  4. Study completionApr 2013

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01184885
Sponsor's protocol ID
09G.474
Other IDs
2009-35, JT 1505
Status last verified
May 2025
First submitted
17 Aug 2010
Last updated
4 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Hyper-CVAD and Sirolimus in people with Lymphoid Malignancies (New or Relapsed) and Acute Lymphoblastic Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 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 16 inclusion and 27 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 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

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?

Yes. Results are posted in the registry (first posted 3 Jan 2014). 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?

Number of Participants With Count Recovery That Allows for Starting a Phase II Study to Evaluate Response Rates and Survival (time frame: 18 months). 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 NCT01184885.

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 4 May 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in