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Acute Undifferentiated LeukemiaPhase 1/2NCT00061945

Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

A Phase 1/2 study testing allopurinol, cyclophosphamide and daunorubicin hydrochloride in people with Acute Undifferentiated Leukemia and B-cell Adult Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

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

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with untreated acute lymphoblastic leukemia. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
allopurinol, cyclophosphamide and daunorubicin hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
302 participants
Where
1 siteUnited States
Study dates
Jun 2003to Oct 2012
Phase
Phase 1/2
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 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Unequivocal histologic diagnosis of precursor B or precursor T lymphoblastic leukemia (World Health Organization [WHO] classification), L1 or L2 ALL or acute undifferentiated leukemia (AUL) (French-American-British Cooperative group [FAB] Classification); Burkitt-type ALL (FAB L3, surface immunoglobulin [SIg]+) are excluded
  • No prior treatment for leukemia with three permissible exceptions:
  • Emergency leukapheresis II. Emergency treatment for hyperleukocytosis with hydroxyurea III. Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
  • All patients must have a pre-treatment bone marrow or peripheral blood sample submitted for central immunophenotyping; only those patients who express CD52 >= 10% in the leukemia blast cell channel will be eligible to receive Campath-1H during module D, course IV

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cancer and Leukemia Group B

    Chicago, Illinois, 60606

Other trials in United States

About this study

Official title: A Phase I/II Dose Escalation Study of Subcutaneous Campath-1H (NSC #715969, IND #10864) During Intensification Therapy in Adults With Untreated Acute Lymphoblastic Leukemia (ALL)

This phase I/II trial studies the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with untreated acute lymphoblastic leukemia. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy also work in different ways to kill cancer cells or stop them from growing. Giving alemtuzumab together with combination chemotherapy may be a better way to block cancer growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the feasibility and toxicity profiles of escalating doses of Campath-1H (alemtuzumab) given subcutaneously during post-remission intensification treatment of adults with acute lymphoblastic leukemia (ALL).

II. To determine the disease-free survival (DFS) and overall survival (OS) when Campath-1H is used during post-remission intensification treatment of adults with ALL.

III. To determine whether antibody treatment with Campath-1H can further reduce minimal residual disease states in adult ALL.

IV. To obtain preliminary descriptive data on serum levels of Campath-1H during course IV, module D using limited pharmacokinetic sampling during the phase I and II components of the study.

  1. To obtain feasibility data on the addition of imatinib to Cancer and Leukemia Group B (CALGB) induction and postremission combination chemotherapy for patients with Philadelphia chromosome positive (Ph+) ALL.

OUTLINE: This is a dose-escalation study of alemtuzumab.

COURSE 1 (module A): Patients receive allopurinol orally (PO) 4 times daily (QID) on days 1-14, cyclophosphamide* intravenously (IV) over 15-30 minutes on day 1, daunorubicin hydrochloride IV on days 1-3, vincristine sulfate IV on days 1, 8, 15, and 22, dexamethasone PO twice daily (BID) on days 1-7 and 15-21, asparaginase subcutaneously (SC) on days 5, 8, 11, 15, 18, and 22, and filgrastim SC on days 4-11. Patients who are Ph+ also receive imatinib mesylate PO on days 15-28.

*Note: Patients who are = 60 years old do not receive cyclophosphamide.

COURSE 2 (module B): Patients receive methotrexate intrathecally (IT) on day 1, cytarabine IV over 3 hours on days 1-3, dexamethasone as eye drops QID on days 1-4, trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-29, and cyclophosphamide, asparaginase and filgrastim as in course 1. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28.

COURSE 3 (module C): Patients receive vincristine sulfate IV on days 1, 15, and 29, methotrexate IV over 3 hours and IT on days 1, 15, and 19, methotrexate PO every 6 hours on days 1-2, 15-16, and 29-30, mercaptopurine PO on days 1-35, leucovorin calcium IV on days 2, 16, and 30, leucovorin calcium PO every 6 hours on days 3-4, and trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-43. Patients who are Ph+ also receive imatinib mesylate PO on days 1-42.

COURSE 4 (module D): Patients receive alemtuzumab SC 3 times weekly for 4 weeks and begin acyclovir PO QID for 6 months (continuing through course 8).

  • Phase I Cohort 1: 10 mg
  • Phase I Cohort 2: 20 mg
  • Phase I Cohort 3/Phase II MTD: 30 mg

COURSE 5 (module A): Patients repeat course 1, minus allopurinol.

COURSE 6 (module B): Patients repeat course 2.

COURSE 7 (module C): Patients repeat course 3.

COURSE 8: Patients receive mercaptopurine PO, vincristine sulfate IV on day 1, dexamethasone PO on days 1-5, methotrexate PO on days 1, 8, 15, and 22, and trimethoprim-sulfamethoxazole PO BID 3 days weekly. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 10 years.

Being tested
allopurinol, cyclophosphamide, daunorubicin hydrochloride, vincristine sulfate, dexamethasone
Medical subject headings
Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

Study groups in NCT00061945
Study groupRoleWhat they receive
Treatment (alemtuzumab and combination chemotherapy)ExperimentalSee detailed description.
Receives: Drug: allopurinol; Drug: cyclophosphamide; Drug: daunorubicin hydrochloride; Drug: vincristine sulfate; Drug: dexamethasone; Drug: asparaginase; Biological: filgrastim; Drug: imatinib mesylate; Drug: methotrexate; Drug: cytarabine; Drug: trimethoprim-sulfamethoxazole; Drug: mercaptopurine; Drug: leucovorin calcium; Biological: alemtuzumab; Drug: acyclovir; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I)

    The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data.

    Measured: 6 weeks

  2. Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II)

    The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV.

    Measured: 8 months

Secondary outcomes (3)

  1. Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II)

    Minimal Residual Disease measures the presence of of circulating leukemia cells in the body. Patients that report a Complete Response (CR) during treatment are further tested to determine the presence of small amounts of circulating leukemia cells. Here we report the number of patients who were MRD negative.

    Measured: 9 years 4 months

  2. Disease-free Survival, for Only Complete Response Patients

    Disease Free Survival (DFS) is defined as the time from a Complete Response (CR) until death or relapse. The date of last clinical assesment will be used as the censor date for patients with no death or relapse. The DFS will be estimated using the Kaplan-Meier method with confidence intervals presented.

    Measured: 9 years 4 months

  3. Overall Survival

    Overall Survival is defines as the time from registration to death due to any cause. It is estimated using the Kaplan-Meier method with confidence intervals presented.

    Measured: 9 years 4 months

Timeline

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

  1. First posted6 Jun 2003 (estimated)
  2. Study startJun 2003
  3. Primary completionDec 2007
  4. Study completionOct 2012

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
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
302 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00061945
Sponsor's protocol ID
NCI-2012-02807
Other IDs
NCI-2012-02807, CDR302482, CALGB 10102, CALGB-10102, U10CA031946
Status last verified
Apr 2022
First submitted
5 Jun 2003
Last updated
3 May 2022

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing allopurinol, cyclophosphamide and daunorubicin hydrochloride in people with Acute Undifferentiated Leukemia and B-cell Adult Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) 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 4 inclusion and 0 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 3 May 2022. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 16 Apr 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?

Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I) (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 NCT00061945.

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 3 May 2022.

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