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

NCT01184885 | Completed Early Phase 1 Results DMC FDA Drug

• 3 other identifiers: 09G.4742009-35JT 1505
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief 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 response rates and survival in adults with Acute Lymphoblastic Leukemia (ALL) and aggressive lymphoid malignancies.

Conditions

Lymphoid Malignancies (New or Relapsed); Acute Lymphoblastic Leukemia; Burkitt Lymphoma; Lymphoblastic Lymphoma; Mantle Cell Lymphoma; Adult T-cell Leukemia/Lymphoma

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

Outcome Measures

Primary Outcomes (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.

  18 months

Secondary Outcomes (2)

• Induction Mortality

  18 months

• Complete Response

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

Study Arms (1)

Hyper-CVAD and Sirolimus

EXPERIMENTAL

Hyper-CVAD and Sirolimus

Drug: Hyper-CVAD; Drug: Sirolimus

Interventions

Hyper-CVAD DRUG

* 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.

Also known as: Cytoxan, Endoxan, Neosar, Procytox, Revimmune, Cytophosphane, Oncovin, Leurocristine, Adriamycin, Hydroxydaunorubicin, MTX, Amethopterin

Hyper-CVAD and Sirolimus

Sirolimus DRUG

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)

Also known as: Rapamycin

Hyper-CVAD and Sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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:
• 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)

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• American Society of Clinical Oncology: collaborator

Study Sites (2)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Lymphoma, Mantle-Cell; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

CVAD protocol; Cyclophosphamide; Vincristine; Doxorubicin; Methotrexate; Sirolimus

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Macrolides; Lactones

Results Point of Contact

• Title: Margaret Kasner, MD
• Organization: Thomas Jefferson University

Margaret.Kasner@jefferson.edu

215-955-8874

Study Officials

• Margaret Kasner, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 19, 2010
• Study Start: July 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: April 1, 2013
• Last Updated: May 4, 2025
• Results First Posted: January 3, 2014

Record last verified: 2025-05

Locations

US (2)