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LeukemiaPhase 1/2NCT00556452

Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen

A Phase 1/2 study testing Clofarabine/Busulfan x 4, Peripheral blood stem cell transplant and Total Lymphoid Irradiation in people with Leukemia and Hodgkin Lymphoma, run by University of Michigan Rogel Cancer Center 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

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity conditioning (Clo/BU4 regimen) prior to transplant and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for stem cell transplant in the treatment of… Read more about this study

Who is it for?
Ages Up to 70 years
Conditions the study is for
Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma
What is being tested?
Clofarabine/Busulfan x 4, Peripheral blood stem cell transplant and Total Lymphoid Irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
Oct 2007to Sep 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 Up to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Disease Criteria
  • Acute leukemia or chronic myelogenous leukemia in blastic crisis or accelerated phase, not in remission at the time of transplant
  • Myelodysplastic syndrome, with more than 5% blasts in bone marrow at the time of transplant
  • Hodgkin and Non-Hodgkin Lymphomas: Not in CR in PET scan or CT scan before transplant, or relapsed within 1 year from previous remission
  • CLL not in remission
  • Multiple Myeloma, not in remission
Show all 15Show fewer
  • Suitable donor available (related or unrelated)
  • Age, Organ Function Criteria
  • Age: ≤ 70 years
  • Cardiac: LV Ejection Fraction ≥ 40% by MUGA or Echocardiogram
  • Pulmonary: FEV1 and FVC ≥ 40% predicted, and DLCO (corrected for hemoglobin) ≥ 40% of predicted
  • Renal: Adult population: serum creatinine ≤ 1.0 mg/dL (if serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation)
  • Renal: Pediatric population: serum creatinine clearance ≥ 90 ml/min/1.73 m2 as calculated by the Schwartz formula for estimated GFR
  • Hepatic: serum total bilirubin ≤ 2.0 mg/dl and AST / ALT ≤ ULN x 4
  • Performance status: Karnofsky ≥ 70%

Who cannot join

  • Other active life-threatening cancer requiring treatment other than allo-HSCT
  • HIV1 or HIV2 positive
  • Uncontrolled medical or psychiatric disorder
  • Uncontrolled viral or fungal infection
  • Active CNS leukemia
  • Non-compliant to medications
  • No appropriate caregivers identified

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

    Ann Arbor, Michigan, 48170

Other trials in United States

About this study

Official title: Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity conditioning (Clo/BU4 regimen) prior to transplant and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for stem cell transplant in the treatment of aggressive hematologic malignancies in subjects where more conventional approaches are failing.

Read the detailed description

Transplants with stem cells collected from the blood of an unrelated donor (allo-HSCT) are being used more commonly for many blood cancers which are not curable with more conventional methods of chemotherapy. Although allo-HSCT has great potential, there are still high risks due to infections, graft-versus-host disease (GVHD), where the donor's cells attack the recipient's tissues as foreign, and due to toxic effects of the chemotherapy drugs given to prepare (or condition) the recipient's bone marrow for transplant.

As a reduced intensity conditioning, a combination of Fludarabine and a lower dose of Busulfan (Flu/BU2) is one of the most popular regimens. Among full-intensity regimens, a combination of Fludarabine and standard-dose Busulfan (Flu/BU4) has been investigated recently and shown to be very well tolerated.

Clofarabine, similar to Fludarabine, is known to have a stronger anti-tumor effect than Fludarabine and has shown promise in treating aggressive acute leukemias. In addition, evidence is that it is well-tolerated with manageable side effects especially in older subjects. Thus replacing Fludarabine with Clofarabine in a full-intensity transplant regimen, Clo/BU4 may provide a regimen with increased anti-tumor activity without adding significant risks of toxicity.

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity regimen (Clo/BU4) and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for HSCT in the treatment for aggressive hematologic malignancies, in subjects where more conventional approaches are failing.

Being tested
Clofarabine/Busulfan x 4, Peripheral blood stem cell transplant, Total Lymphoid Irradiation
Medical subject headings
Leukemia, Hodgkin Disease, Lymphoma, Non-Hodgkin, Multiple Myeloma, Myelodysplastic Syndromes

What participants receive

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

  • Clofarabine/Busulfan x 4Drug

    Clofarabine IV (dose levels)

    • 1st dose level: 20 mg/m2/day x 5 days
    • 2nd dose level: 30 mg/m2/day x 5 days
    • 3rd dose level: 40 mg/m2/day x 5 days

    Busulfan IV 3.2 mg/kg daily x 4 days

  • Peripheral blood stem cell transplantProcedure or surgery

    Peripheral blood stem cell transplant, after pre-conditioning drug treatment

  • Total Lymphoid IrradiationRadiation

    Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

Study groups in NCT00556452
Study groupRoleWhat they receive
Clo/BU4ExperimentalStudy will start at the 2nd dose level of three Clofarabine levels, in combination with Busulfan. The Clofarabine level that each subsequent patient is treated at is determined by a method using continual reassessment. After pre-conditioning, subjects will receive a peripheral blood stem cell transplant.
Receives: Drug: Clofarabine/Busulfan x 4; Procedure: Peripheral blood stem cell transplant; Radiation: Total Lymphoid Irradiation

What is being measured

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

  1. Regimen Related Toxicities

    The incidence of non-hematological toxicities (Common Terminology Criteria for Adverse Events (CTCAE) 3.0) from initiation of conditioning to Day + 30 or toxicities after day +30, possibly, probably or definitely related to conditioning for all patients treated with Clofarabine (independent of dose level).

    Measured: two years

  2. One-year Overall Survival Rate for AML

    Percent Overall Survival (OS) for at one year for subjects with Acute Myeloid Leukemia (AML).

    Measured: 1 year

Secondary outcomes (2)

  1. Two-year Overall Survival for All Cases.

    Percent Overall Survival (OS) at two years for all patients.

    Measured: 2 years

  2. Five Year Overall Survival for All Cases

    The number of patients alive at 5 years

    Measured: five years

Timeline

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

  1. First posted12 Nov 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionJun 2011
  4. Study completionSep 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
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00556452
Sponsor's protocol ID
UMCC 2007.055
Status last verified
Oct 2017
First submitted
8 Nov 2007
Last updated
5 Dec 2017
Data monitoring committee
No

Publications

  • Magenau J, Tobai H, Pawarode A, Braun T, Peres E, Reddy P, Kitko C, Choi S, Yanik G, Frame D, Harris A, Erba H, Kujawski L, Elenitoba-Johnson K, Sanks J, Jones D, Paczesny S, Ferrara J, Levine J, Mineishi S. Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies. Blood. 2011 Oct 13;118(15):4258-64. doi: 10.1182/blood-2011-06-358010. Epub 2011 Aug 12.

    PubMed 21841163

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Clofarabine/Busulfan x 4, Peripheral blood stem cell transplant and Total Lymphoid Irradiation in people with Leukemia and Hodgkin Lymphoma, run by University of Michigan Rogel Cancer Center 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 15 inclusion and 7 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 5 Dec 2017. 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 13 Jan 2015). 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?

Regimen Related Toxicities (time frame: two years). 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 NCT00556452, which also lists 1 linked publication.

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 5 Dec 2017.

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