Chronic Myeloid LeukemiaPhase 2CMLNCT00531310
Reduced Intensity AlloSCT in(CML) With Persistent Disease
A Phase 2 study testing Reduced Intensity Conditioning, Busulfan and Fludarabine in people with Chronic Myeloid Leukemia, run by Columbia University at 1 site in United States.
Trial summary
CML, a malignant disorder of stem cells, is characterized by increases in both immature and mature myeloid, erythroid, and lymphoid cells, as well as platelets in the peripheral blood. The cytogenetic hallmark of CML is the Philadelphia(Ph)chromosome found in the malignant cells of 95% of patients. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Reduced Intensity Conditioning, Busulfan and Fludarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to Jun 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Patient must be less than 30 years of age.
- Consent: Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
- Organ Function: Patient must have adequate organ function as below Adequate renal function defined as:Serum creatinine 1.5 x normal, or Creatinine clearance or radioisotope GFR > 40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
- Adequate liver function defined as:Total bilirubin < 2.5 x normal; or SGOT (AST) or SGPT (ALT) < 5.0 x normal
- Adequate cardiac function defined as:
- Shortening fraction of >25% by echocardiogram, or
Show all 13Show fewer
- Ejection fraction of >40% by radionuclide angiogram or echocardiogram
- Adequate pulmonary function defined as:
- -DLCO >40% by pulmonary function test For children who are uncooperative, no evidence of dyspnea at rest,no exercise intolerance, and a pulse oximetry >94% in room air.
- Disease Status
- Patients with CML with either of the following:
- Patients in 1st or 2nd chronic phase
- Patients in 1st or 2nd accelerated phase
Who cannot join
- Patient in blast crisis
- Patient in 3rd or greater chronic phase
- Patient in 3rd or greater accelerated phase
- women that are pregnant are ineligible
Trial locations and contacts
1 site in 1 country.
United States1 site
Morgan Stanley Children's Hospital of NYP
New York, New York, 10032
About this study
Official title: A Pilot Study of Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Chronic Myeloid Leukemia (CML) and Adoptive Cellular Immunotherapy Only in Patients With Persistent Disease and Matched Family Donors
CML, a malignant disorder of stem cells, is characterized by increases in both immature and mature myeloid, erythroid, and lymphoid cells, as well as platelets in the peripheral blood. The cytogenetic hallmark of CML is the Philadelphia(Ph)chromosome found in the malignant cells of 95% of patients. CML comprises 7-20% of all leukemias with an overall incidence in the general population estimated at 1 to 2 per 100,000. The peak incidence occurs in the fifth decade, however, all age groups, including children, are affected. The only reported environmental risk factor is exposure to excessive ionizing radiation that is documented in only a very small percentage of patients. Clinically, CML is characterized by an initial chronic phase in which patients may report mild constitutional symptoms; however, 40-50% are asymptomatic and are diagnosed based upon abnormal blood counts discovered during a routine examination. The chronic phase typically lasts three to five years, and is followed by an accelerated phase distinguished by progressive systemic symptoms, an increasing resistance to conventional chemotherapy, and a rise in the peripheral blood and bone marrow blast count. This evolves rapidly into a blastic crisis characterized by immature cells resembling the blasts characteristic of acute leukemia. The presence of 30% or more blastic cells in the blood or marrow is diagnostic of this final blastic phase which is typically fatal within 3 to 6 months.
The primary treatment options for CML have traditionally been monotherapy with either busulfan or hydroxyurea. Both agents are able to control the clinical symptoms associated with CML, as well as induce hematological remissions in 80% of chronic phase patients. However, complete cytogenetic remissions with either agent are rare, and neither is able to prevent eventual progression to the terminal blastic phase; therefore, these therapies can only be considered palliative.
The primary purpose of this clinical research trial is to study the feasibility of a reduced intensity allogenic transplant for CML. This study will also determine the side effects as well as the response rate.
Read the detailed description
Further study details will be provided by Columbia University, Division of Pediatric Blood and Marrow Transplantation.
STUDY DESIGN:
Patients less than 30 years of age with CML in 1st or 2nd chronic phase or 1st accelerated phase and a matched related donor, an unrelated cord blood donor, or an unrelated adult donor, will receive 6 days of IV Fludarabine, 4 doses of IV Busulfex, and 5 doses of Alemtuzumab. Patients with persistant RT-PCR positive BCR-Abl and/or Philadelphia chromosome positivity by cytogentics after Day + 100 and a matched related donor would receive DLIx1. If still BCR-Abl or Philadelphia chromosome positive at Day +180 and a matched related donor, patients would receive a second dose of DLI. All patients will receive STI-571 (Gleevec) after hematological reconstitution. Studies for immune reconstitution, chimersim, and MRD will be performed postt AlloSCT.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Reduced Intensity Conditioning, Busulfan and Fludarabine
- Keywords
- CML, allogeneic SCT, matched family donor, unrelated donor, cord blood donor, persistent disease
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced Intensity Conditioning, Busulfan and FludarabineDrug
Also called RIC
Busulfan and Fludarabine
| Study group | Role | What they receive |
|---|---|---|
| Matched Family Donor | Experimental | Matched Family Donor Receives: Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine |
| Unrelated Donor | Experimental | Unrelated Donor Transplant/ Cord Blood Transplant Receives: Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the toxicity associated with reduced intensity therapy and allogeneic SCT in selected patients with CML.
Measured: Until Study End
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2007 (estimated)
- Study startJan 2003
- Primary completionDec 2007
- Study completionJun 2010
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Investigators
- Mtchell S Cairo, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00531310
- Sponsor's protocol ID
- AAAA8191
- Other IDs
- CHNY-01-505
- Acronym
- CML
- Status last verified
- Apr 2011
- First submitted
- 15 Sep 2007
- Last updated
- 14 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Chronic Myeloid Leukemia (CML) and Adoptive Cellular Immunotherapy Only in Patients With Persistent Disease and Matched Family Donors
- ClinicalTrials.gov ID
- NCT00531310
- Acronym / sponsor ID
- CML / AAAA8191
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- CML, allogeneic SCT, matched family donor, unrelated donor, cord blood donor, persistent disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Jan 2003
- Primary completion
- Dec 2007 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 18 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
CML, a malignant disorder of stem cells, is characterized by increases in both immature and mature myeloid, erythroid, and lymphoid cells, as well as platelets in the peripheral blood. The cytogenetic hallmark of CML is the Philadelphia(Ph)chromosome found in the malignant cells of 95% of patients. CML comprises 7-20% of all leukemias with an overall incidence in the general population estimated at 1 to 2 per 100,000. The peak incidence occurs in the fifth decade, however, all age groups, including children, are affected. The only reported environmental risk factor is exposure to excessive ionizing radiation that is documented in only a very small percentage of patients. Clinically, CML is characterized by an initial chronic phase in which patients may report mild constitutional symptoms; however, 40-50% are asymptomatic and are diagnosed based upon abnormal blood counts discovered during a routine examination. The chronic phase typically lasts three to five years, and is followed by an accelerated phase distinguished by progressive systemic symptoms, an increasing resistance to conventional chemotherapy, and a rise in the peripheral blood and bone marrow blast count. This evolves rapidly into a blastic crisis characterized by immature cells resembling the blasts characteristic of acute leukemia. The presence of 30% or more blastic cells in the blood or marrow is diagnostic of this final blastic phase which is typically fatal within 3 to 6 months.
The primary treatment options for CML have traditionally been monotherapy with either busulfan or hydroxyurea. Both agents are able to control the clinical symptoms associated with CML, as well as induce hematological remissions in 80% of chronic phase patients. However, complete cytogenetic remissions with either agent are rare, and neither is able to prevent eventual progression to the terminal blastic phase; therefore, these therapies can only be considered palliative.
The primary purpose of this clinical research trial is to study the feasibility of a reduced intensity allogenic transplant for CML. This study will also determine the side effects as well as the response rate.
Detailed description
Further study details will be provided by Columbia University, Division of Pediatric Blood and Marrow Transplantation.
STUDY DESIGN:
Patients less than 30 years of age with CML in 1st or 2nd chronic phase or 1st accelerated phase and a matched related donor, an unrelated cord blood donor, or an unrelated adult donor, will receive 6 days of IV Fludarabine, 4 doses of IV Busulfex, and 5 doses of Alemtuzumab. Patients with persistant RT-PCR positive BCR-Abl and/or Philadelphia chromosome positivity by cytogentics after Day + 100 and a matched related donor would receive DLIx1. If still BCR-Abl or Philadelphia chromosome positive at Day +180 and a matched related donor, patients would receive a second dose of DLI. All patients will receive STI-571 (Gleevec) after hematological reconstitution. Studies for immune reconstitution, chimersim, and MRD will be performed postt AlloSCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Matched Family Donor | Experimental | Drug: Reduced Intensity Conditioning, Busulfan and FludarabineMatched Family Donor |
| Unrelated Donor | Experimental | Drug: Reduced Intensity Conditioning, Busulfan and FludarabineUnrelated Donor Transplant/ Cord Blood Transplant |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Age: Patient must be less than 30 years of age.
- Consent: Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
- Organ Function: Patient must have adequate organ function as below Adequate renal function defined as:Serum creatinine 1.5 x normal, or Creatinine clearance or radioisotope GFR > 40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
- Adequate liver function defined as:Total bilirubin < 2.5 x normal; or SGOT (AST) or SGPT (ALT) < 5.0 x normal
- Adequate cardiac function defined as:
Key exclusion criteria (4 listed)
- Patient in blast crisis
- Patient in 3rd or greater chronic phase
- Patient in 3rd or greater accelerated phase
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced Intensity Conditioning, Busulfan and FludarabineAlso: RICBusulfan and Fludarabine | Drug | Matched Family Donor, Unrelated Donor |
Primary outcome
To determine the toxicity associated with reduced intensity therapy and allogeneic SCT in selected patients with CML.
Time frame: Until Study End
Results and safety
The study was stopped early (reason given: Poor accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mtchell S Cairo, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Reduced Intensity Conditioning, Busulfan and Fludarabine in people with Chronic Myeloid Leukemia, run by Columbia University 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 13 inclusion and 4 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: stopped early, as of the sponsor's last update on 14 Apr 2011. 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 phase mean?
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?
The study was stopped early (reason given: Poor accrual). Results are not available in the source record.
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?
To determine the toxicity associated with reduced intensity therapy and allogeneic SCT in selected patients with CML. (time frame: Until Study End). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Apr 2011.