Hematologic MalignanciesPhase 1NCT00824135
Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies
A Phase 1 study testing Clofarabine, Stem Cell Transplantation, Hematopoietic and OKT3 in people with Hematologic Malignancies, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Patients with refractory hematologic malignancies including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- Clofarabine, Stem Cell Transplantation, Hematopoietic and OKT3
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Dec 2016
- Phase
- Phase 1
- 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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age less than or equal to 21 years old; may be greater than 21 years old if a previously treated St. Jude patient and within 3 years of completion of most recent prior disease specific therapy.
- One of the following refractory hematologic malignancies (chemoresistant relapse or primary induction failure) or diagnoses:
- ALL
- AML (>25% blasts in the bone marrow)
- secondary AML/MDS
- CML in accelerated phase or blast crisis
Show all 29Show fewer
- juvenile myelomonocytic leukemia (JMML)
- myelodysplastic syndrome (MDS)
- Hodgkin or non-Hodgkin lymphoma (NHL) with residual or recurrent disease following autologous HSCT, who are unable to undergo autologous HSCT due to chemo-resistant disease or inability to have an acceptable quantity of tumor-free stem cells collected (> 1 x 108 TNC/kg marrow or > 1 x 106 CD34+/kg PBS
- patients with a hematologic malignancy who have undergone prior allogeneic HSCT or who have a co-morbid condition that in the medical opinion of medical faculty (Division of Bone Marrow Transplantation and Cellular Therapy) makes standard myeloablation prohibitive
- Does not have any other active malignancy other than the one for which this transplant is indicated
- Cardiac shortening fraction greater than or equal to 25%
- For pediatric patients, creatinine clearance greater than or equal to 90 ml/min/1.73 m2 according to the Schwartz formula for estimated GFR (ml/min/1.73m2) = k*height (cm)/serum creatinine (mg/dL). k is a proportionality constant that varies with age and is a function of urinary creatinine clearance per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 for adolescent boys
- For adolescent or adult patients, 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 where predicted GFR (ml/min/1.73 m2) = 186 x (serum creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black)
- Forced vital capacity (FVC) greater than or equal to 40% of predicted value or pulse oximetry greater than or equal to 92% on room air.
- Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 50 (See APPENDIX A)
- Does not have active acute or active chronic GVHD defined as requiring medical therapy.
- Does not have active acute bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP).
- Has a suitable HLA partially matched family member donor available for stem cell donation
- Bilirubin less than or equal to 1.5 times the upper limit of normal for age.
- Alanine aminotransferase (ALT) less than or equal to 1.5 times the upper limit of normal for age.
- Aspartate aminotransferase (AST) less than or equal to 1.5 times the upper limit of normal for age.
- Not pregnant (confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment).
- Not lactating
- Partially HLA-matched family member.
- At least 18 years of age.
- HIV negative
- Not pregnant (confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment).
- Not lactating
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38119
About this study
Patients with refractory hematologic malignancies including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. The investigators institution has utilized mismatched family member donors for these patients for several reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor trans-plantation averages 3 to 4 months; (3) the alloimmune reactivity of natural killer (NK) cells following haploidentical HSCT has been shown to reduce relapse rates in certain patient groups; and, (4) no other curative treatment options are available.
In the present trial, the investigators propose a novel conditioning regimen using clofarabine in an effort to enhance cytotoxicity while simultaneously reducing regimen related toxicity. In this phase I trial, the goal is to determine the maximum tolerated dose (MTD) of clofarabine when used in combination with melphalan and thiotepa pre-transplant.
Read the detailed description
The primary objective of this trial is to determine the maximum tolerated dose of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical stem cell transplant with an engineered graft depleted of CD3+ cells. Study participants will children and young adults with refractory hematologic malignancies.
Secondary objectives include the following:
- To describe the one-year overall survival (OS) and event-free survival (EFS) rates in these study participants.
- To determine the time to hematopoietic recovery and donor cell engraftment following this study treatment.
- To estimate the cumulative incidence of relapse in study participants.
- To estimate the incidence of overall grade II-IV and grade III-IV acute GVHD and the rate of chronic GVHD.
- To estimate the incidence and describe the causes of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post HSCT.
- To explore the biologic significance of soluble interleukin-2 (IL-2) receptor, tumor necrosis factor (TNF), and lymphocyte reconstitution (qualitative and quantitative, V beta spectratyping, TREC
- Conditions
- Hematologic Malignancies
- Keywords
- Stem Cell Transplantation, Hematopoietic, Peripheral Blood Stem Cell Transplantation, Maximal Tolerated Dose, Clofarabine, Hematological Malignancies, Apheresis
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofarabineDrug
One dose intravenously every 24 hrs for five days total.
Dose level 1 Clofarabine 40 mg/m2/day intravenous Dose level 2 Clofarabine 45 mg/m2/day intravenous Dose Level 3 Clofarabine 50 mg/m2/day intravenous
Stem Cell Transplantation, HematopoieticProcedure or surgery
Haploidentical Hematopoietic Stem Cell Transplantation (two infusions, one on day 0 and the other on day +1)
OKT3Other
Also called Orthoclone OKT3
Start at 0.0125 mg/kg intravenous once a day, taper dose down incrementally and discontinue after 17 days total
Muromonab-CD3
ThiotepaDrug
5 mg/kg/day intravenous every 12 hours (2 doses total)
MelphalanDrug
60mg/m2 intravenous every 12 hours for 2 doses total.
Also called MMF, CellCept
Mycophenolate mofetil 600 mg/m2 intravenous two times a day
(continue for approximately 2 months or as clinically indicated)
RituximabDrug
Also called Rituxin
375 mg/m2 intravenous for 1 dose total
G-CSFOther
G-CSF 5 mcg/kg/day subcutaneous or intravenous until ANC greater than 2.000/mm3 for 2 consecutive days and then as clinically indicated.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Clofarabine; Procedure: Stem Cell Transplantation, Hematopoietic; Other: OKT3; Drug: Thiotepa; Drug: Melphalan; Drug: Mycophenolate mofetil; Drug: Rituximab; Other: G-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the MTD and DLT of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical HSCT with an engineered graft depleted of CD3+ cells obtained by negative selection with OKT3 on the CliniMACS system.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionOct 2012
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Brandon Triplett, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00824135
- Sponsor's protocol ID
- REFLEX
- Other IDs
- NCI-2011-03677
- Status last verified
- Dec 2016
- First submitted
- 15 Jan 2009
- Last updated
- 2 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00824135
- Acronym / sponsor ID
- REFLEX
- Conditions
- Hematologic Malignancies
- Keywords
- Stem Cell Transplantation, Hematopoietic, Peripheral Blood Stem Cell Transplantation, Maximal Tolerated Dose, Clofarabine, Hematological Malignancies, Apheresis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Jan 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 16 Jan 2009 (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.
Patients with refractory hematologic malignancies including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. The investigators institution has utilized mismatched family member donors for these patients for several reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor trans-plantation averages 3 to 4 months; (3) the alloimmune reactivity of natural killer (NK) cells following haploidentical HSCT has been shown to reduce relapse rates in certain patient groups; and, (4) no other curative treatment options are available.
In the present trial, the investigators propose a novel conditioning regimen using clofarabine in an effort to enhance cytotoxicity while simultaneously reducing regimen related toxicity. In this phase I trial, the goal is to determine the maximum tolerated dose (MTD) of clofarabine when used in combination with melphalan and thiotepa pre-transplant.
Detailed description
The primary objective of this trial is to determine the maximum tolerated dose of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical stem cell transplant with an engineered graft depleted of CD3+ cells. Study participants will children and young adults with refractory hematologic malignancies.
Secondary objectives include the following:
- To describe the one-year overall survival (OS) and event-free survival (EFS) rates in these study participants.
- To determine the time to hematopoietic recovery and donor cell engraftment following this study treatment.
- To estimate the cumulative incidence of relapse in study participants.
- To estimate the incidence of overall grade II-IV and grade III-IV acute GVHD and the rate of chronic GVHD.
- To estimate the incidence and describe the causes of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post HSCT.
- To explore the biologic significance of soluble interleukin-2 (IL-2) receptor, tumor necrosis factor (TNF), and lymphocyte reconstitution (qualitative and quantitative, V beta spectratyping, TREC
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Clofarabine, Procedure: Stem Cell Transplantation, Hematopoietic, Other: OKT3, Drug: Thiotepa, Drug: Melphalan, Drug: Mycophenolate mofetil, Drug: Rituximab, Other: G-CSF |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (29 listed)
- Age less than or equal to 21 years old; may be greater than 21 years old if a previously treated St. Jude patient and within 3 years of completion of most recent prior disease specific therapy.
- One of the following refractory hematologic malignancies (chemoresistant relapse or primary induction failure) or diagnoses:
- ALL
- AML (>25% blasts in the bone marrow)
- secondary AML/MDS
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| ClofarabineOne dose intravenously every 24 hrs for five days total. Dose level 1 Clofarabine 40 mg/m2/day intravenous Dose level 2 Clofarabine 45 mg/m2/day intravenous Dose Level 3 Clofarabine 50 mg/m2/day intravenous | Drug | 1 |
| Stem Cell Transplantation, HematopoieticHaploidentical Hematopoietic Stem Cell Transplantation (two infusions, one on day 0 and the other on day +1) | Procedure or surgery | 1 |
| OKT3Also: Orthoclone OKT3Start at 0.0125 mg/kg intravenous once a day, taper dose down incrementally and discontinue after 17 days total Muromonab-CD3 | Other | 1 |
| Thiotepa5 mg/kg/day intravenous every 12 hours (2 doses total) | Drug | 1 |
| Melphalan60mg/m2 intravenous every 12 hours for 2 doses total. | Drug | 1 |
| Mycophenolate mofetilAlso: MMF, CellCeptMycophenolate mofetil 600 mg/m2 intravenous two times a day (continue for approximately 2 months or as clinically indicated) | Drug | 1 |
| RituximabAlso: Rituxin375 mg/m2 intravenous for 1 dose total | Drug | 1 |
| G-CSFG-CSF 5 mcg/kg/day subcutaneous or intravenous until ANC greater than 2.000/mm3 for 2 consecutive days and then as clinically indicated. | Other | 1 |
Primary outcome
To determine the MTD and DLT of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical HSCT with an engineered graft depleted of CD3+ cells obtained by negative selection with OKT3 on the CliniMACS system.
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2017.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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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.
Brandon Triplett, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clofarabine, Stem Cell Transplantation, Hematopoietic and OKT3 in people with Hematologic Malignancies, run by St. Jude Children's Research Hospital 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 29 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 2 Jan 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 MTD and DLT of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical HSCT with an engineered graft depleted of CD3+ cells obtained by negative selection with OKT3 on the CliniMACS system. (time frame: 30 days). 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 2 Jan 2017.