CalPeg for Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

February 12, 2024 updated by: H. Lee Moffitt Cancer Center and Research Institute

A Single-Arm, Open-Label Phase 1b Study of Hyper-CVAD + Calaspargase Pegol in Young Adults With Newly Diagnosed Acute Lymphoblastic Leukemia

The purpose of the study is to evaluate the safety and tolerability of the study drug, calaspargase pegol, when given with multi-agent chemotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Bijal Shah, MD
        • Sub-Investigator:
          • Julio Chavez, MD, MS
        • Sub-Investigator:
          • Sameh Gaballa, MD
        • Sub-Investigator:
          • Leidy Isenalumhe, MD, MS
        • Sub-Investigator:
          • Hayder Saeed, MD
        • Sub-Investigator:
          • Lubomir Sokol, MD, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically confirmed Philadelphia negative B- or T-cell acute lymphoblastic leukemia, with >10% peripheral blood or bone marrow lymphoblasts at diagnosis.
  • Treatment and full recovery from arm 1A of the Hyper-CVAD regimen.
  • Be willing and able to provide written informed consent/assent for the trial.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Cardiac ejection fraction ≥ 50% by echocardiography or MUGA, as measured prior to arm 1A of Hyper-CVAD.
  • Serum bilirubin and creatinine < 1.5x upper limit of normal (ULN). AST and ALT must be <3x ULN.
  • Females of childbearing potential (FCBP) must have a negative serum pregnancy test at screening. A FCBP is considered when a sexually mature female: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months.
  • A FCBP must agree to use of two methods of highly effective non-hormonal contraception, be surgically sterile, or abstain from heterosexual activity for the course of the study through 3 monthsafter the last dose of study treatment.
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 30 days after the last dose of study therapy. Men must agree to not donate sperm during and after the study for 3 months

Exclusion Criteria:

  • Induction therapy with any regimen other than Hyper-CVAD 1A.
  • Diagnosis of L3 type Burkitt's lymphoma
  • Clinical evidence of active central nervous system (CNS) leukemia.
  • Any major surgery or radiation therapy within four weeks.
  • Diagnosis of Down Syndrome.
  • Any active infection requiring systemic therapy, including HIV, Hepatitis B, and/or Hepatitis C.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator (including but not limited to unstable angina, pre-existing liver disease, recurrent pancreatitis, uncontrolled diabetes, hypertriglyceridemia, pulmonary hypertension, or severeheart failure (New York Heart Association Class III-IV).
  • Recurrent thrombosis, or non-central venous catheter associated thrombosis within 3 months prior to enrollment.
  • Severe comorbid conditions for which life expectancy would be <6 months.
  • Patients with active (uncontrolled, metastatic) second malignancies are excluded.
  • Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 3 months after the last dose of trial treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hyper-CVAD + Calaspargase pegol Treatment
Participants will receive calaspargase pegol administered over 1 hour with each cycle of Hyper-CVAD, mini-CVD, and late intensification, beginning with Cycle 1B. Responding patients will have dose reduction of HyperCVAD for Cycles 2B-4B. Participants with CD20+ ALL will also be given Rituximab once per cycle.
Drug: Hyper CVAD Protocol (Standard of Care Multi-Agent Chemotherapy)

Hyper-CVAD consists of two combinations of drugs (courses A and B) given in an alternating fashion. The term "hyper" refers to the hyperfractionated nature of the chemotherapy, which is given in small doses, more frequently, to minimize side effects. CVAD is the acronym of the drugs in course a: cyclophosphamide, vincristine, doxorubicin and dexamethasone.

Course A: Cyclophosphamide days 1, 2 and 3. Vincristine days 4 and 11, Doxorubicin day 4, dexamethasone days 1-4 and 11-14, Cytarabine day 7. Mesna is also given orally with cyclophosphamide, to reduce the incidence of haemorrhagic cystitis, a common side effect of cyclophosphamide. Methotrexate, an antimetabolite, may be given when necessary to get chemotherapy past the blood brain barrier.

Course B: Methotrexate Day 1 and Cytarabine Days 2 and 3. Dosage is individualized to the patient.

Drug: Calaspargase Pegol
Calaspargase pegol 2000 IU/m^2 (capped at 3750 IU) will be administered beginning in cycle 1B of Hyper-CVAD, and will continue at this dose for the duration of the trial.
Other Names:
  • Asparlas
  • CalPeg
Drug: Rituximab
Rituximab 375mg/m^2 will be administered once per cycle for patients with CD20+ ALL.
Other Names:
  • Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality Rate of Hyper-CVAD after first infusion of calaspargase pegol
Time Frame: Up to 12 months
Mortality rate is hypothesized to be less than 10% when combining calaspargase pegol with Hyper-CVAD.
Up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimal Residual Disease Remission Rate
Time Frame: Up to 3 years
Minimal Residual Disease (MRD) will be studied as a dichotomous endpoint using a cutoff of 1x10^4 cells/transcripts as the lower limit for residual leukemia and presented as the percentage of patients reaching this landmark as their best response. MRD assessment will be obtained with each bone marrow biopsy assessment, every 3 months in the first year following their last cycle of therapy and every 6 months in the subsequent 2 years following their last cycle.
Up to 3 years
Progression Free Survival
Time Frame: Up to 42 months
Progression Free Survival defined as the time from start of treatment to the time of progression or death.
Up to 42 months
Overall Survival
Time Frame: Up to 42 months
Overall Survival (OS) will be measured from the initial date of treatment to the recorded date of death.
Up to 42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Servier

Investigators

  • Principal Investigator: Bijal Shah, MD, Moffitt Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2023

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

November 1, 2027

Study Registration Dates

First Submitted

October 12, 2022

First Submitted That Met QC Criteria

October 12, 2022

First Posted (Actual)

October 14, 2022

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 12, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-21213

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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