Hematologic MalignancyPhase 1/2NCT00056966
Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases
A Phase 1/2 study testing ANTI-CD45, CAMPATH-1H and FK506 in people with Hematologic Malignancy, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Participants in this study have a hematologic malignancy (a disorder in the bone marrow that affects the body's ability to create blood) that might benefit from receiving an allogeneic stem cell transplant (meaning the cells come from a donor) from a family member or nearly identical matched donor. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hematologic Malignancy
- What is being tested?
- ANTI-CD45, CAMPATH-1H and FK506
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2002to Dec 2006
- Phase
- Phase 1/2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with one of the following high risk diseases needing allogeneic hemopoietic stem cell transplantation:
- Acute myeloid leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
- Acute lymphoblastic leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
- Chronic myeloid leukemia, either a) Accelerated phase, or b) Blast crisis, or c) Chronic phase and not achieving major cytogenetic response despite standard therapy
- Chronic lymphocytic leukemia, either a) Primary refractory, or b) Beyond first complete remission(CR1),
- Non Hodgkin's lymphoma, either a) Primary refractory, or b) Beyond first complete remission(CR1)
Show all 24Show fewer
- Hodgkin's disease, either a) Primary refractory, or b) Beyond first complete remission(CR1),
- Myelodysplastic syndrome with IPSS score > 0. (Appendix A)
- Myeloproliferative disorders (with the exclusion of chronic myeloid leukemia) a) Primary Myelofibrosis with Lile score of 1 or 2 (Appendix B) b) Polycythemia Vera or Essential Thrombocythemia transformed to AML or Myelofibrosis and PV "spent phase"
- Multiple Myeloma with stage II or III disease
- Severe aplastic anemia
- Conditions that increase Treatment Related Mortality (need one or more to be eligible):
- Greater or equal to 35 years of age;
- Ejection Fraction of less than 50%;
- DLCO less than 50% or FEV1/FVC < 80% of predicted value;
- Diabetes Mellitus;
- Renal insufficiency (serum creatinine abnormal);
- Hepatic dysfunction-transaminases, or alkaline phosphatase, or bilirubin twice the upper limit of normal;
- Prior recent history of systemic fungal infection;
- Multiple prior treatment regimens (equal to or more than 3);
- Significant Grade III or IV neurologic, cardiac, pulmonary, renal or hepatic toxicity from previous treatment;
- Prior Autologous or Allogeneic Stem Cell transplantation;
- Available Healthy Donor without any contraindications for donation. 5/6 or 6/6 related or unrelated donor (molecular typing for DRB1);
- Patient and/or responsible person able to understand and sign consent
Who cannot join
- Pregnant and lactating women, or women unwilling to use contraception.
- HIV positive patient
- Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater)
- Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater)
- Child's class C cirrhosis
- Unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months)
- Patients with known allergy to rat serum products
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Children's Hospital
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
About this study
Official title: Phase I/II Study of CD45 Antibodies and Alemtuzumab Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases
Participants in this study have a hematologic malignancy (a disorder in the bone marrow that affects the body's ability to create blood) that might benefit from receiving an allogeneic stem cell transplant (meaning the cells come from a donor) from a family member or nearly identical matched donor. The donor may either be a matched sibling, a mismatched family member, or an unrelated person.
Usually these patients are given high doses of chemotherapy before receiving a stem cell transplant to keep their immune system from rejecting the donor stem cells and to kill any diseased cells that remain in the body. However, this group of patients have a high risk of developing possibly life-threatening treatment-related side effects such as infections, damage to vital organs such as lungs, liver, kidney and heart, as well as graft versus host disease (GVHD).
Instead of the high dose chemotherapy and radiotherapy usually given before a transplant, this research study uses a new pre-transplant combination of three drugs, Fludarabine, Anti-CD45 and CAMPATH-1H with low dose radiotherapy. Fludarabine is a chemotherapy drug while Anti-CD45 and CAMPATH-1H are antibodies against certain types of blood cells, including those which are causing this disease. CAMPATH-1H is particularly important because it stays active in the body for a long time after it is given, which means it may work longer to prevent GVHD symptoms. Anti-CD45 may help in eradicating residual malignant cells. All these agents also help in preventing rejection of donor stem cells. This study is designed to give a less intense chemotherapy and radiotherapy, so that the life-threatening toxicities of conventional high dose chemotherapy and radiotherapy regimen can be reduced, while maintaining the ability to cure cancer.
Read the detailed description
CAMPATH-1H will be given as a daily IV infusion for three days. Fludarabine will be given as a daily IV infusion for four days. Anti-CD45 will be given as a daily IV infusion for 4 days. Patients will then receive radiotherapy (also known as Total Body Irradiation or TBI) for one day. A summary of the treatment follows:
- Day - 8: CAMPATH-1H and Fludarabine
- Day - 7: CAMPATH-1H and Fludarabine
- Day - 6: CAMPATH-1H and Fludarabine
- Day - 5: Anti-CD45 and Fludarabine
- Day - 4: Anti-CD45
- Day - 3: Anti-CD45
- Day - 2: Anti-CD45
- Day - 1: TBI
- Day 0: Stem Cell Infusion (transplant)
To help prevent the body from developing GVHD, patients will also receive the drug FK506, starting two days before the transplant and continuing for at least one month.
Both the CAMPATH-1H and the Anti-CD45 can cause allergic reactions so patients will be given drugs to help prevent those reactions before receiving daily doses.
To see how CAMPATH-1H works in patients with hematologic malignancies, some patients will be asked to participate in pharmacokinetic studies. For this, approximately 13 blood samples will be taken from the central line scheduled before each infusion on Day -8 to Day -6, daily thereafter until Day 0, and then approximately once per week on days 7, 14, 21 and 28 post transplant. No more than 5 teaspoonfuls total will be drawn.
To see how Anti-CD45 works in patients with hematologic malignancies some patients will be asked to participate in pharmacokinetic studies. Approximately 22 blood samples will be taken from the central line scheduled before, during and after each infusion and after the end of the last infusion of Anti-CD45. No more than 10 teaspoonfuls total will be drawn over the course of the four anti-CD45 infusions.
- Conditions
- Hematologic Malignancy
- Being tested
- ANTI-CD45, CAMPATH-1H, FK506, Fludarabine, Total Body Irradiation
- Keywords
- Acute myeloid leukemia, Acute lymphoblastic leukemia, Chronic myeloid leukemia, Non-Hodgkin's lymphoma, Hodgkin's disease, Myelodysplastic syndrome, Myeloproliferative disorders, Multiple myeloma, Severe aplastic anemia
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Non-Hodgkin, Hodgkin Disease, Myelodysplastic Syndromes, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANTI-CD45Drug
400ug/kg Day-5 through Day-2
CAMPATH-1HDrug
Also called anti-CD52, alemtuzumab
Day -8 through Day -6 Dosed per Institutional SOP
FK506Drug
Also called tacrolimus
Day -2 through Day 30 dose adjusted to maintain level between 5-15 ng/ml.
FludarabineDrug
Day-8 through Day-5 30 mg/m2
Total Body IrradiationRadiation
Day-1 single dose 450 cGy
Stem cell infusionProcedure or surgery
Patients will receive peripheral blood stem cells from a HLA matched or one antigen mismatched related or unrelated donor (target CD34+ cell count >2 x 106/kg). When peripheral stem cells are unavailable or insufficient, bone marrow (target mononuclear cell count >2 x 108/kg) will be substituted.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | recipients of HLA matched sibling transplants Receives: Drug: ANTI-CD45; Drug: CAMPATH-1H; Drug: FK506; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Stem cell infusion |
| 2 | Experimental | recipients of unrelated or mismatched family donor transplants Receives: Drug: ANTI-CD45; Drug: CAMPATH-1H; Drug: FK506; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Stem cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess safety and feasibility of monoclonal abs directed to CD45 and CD52 antigens, Fludarabine and low dose TBI, as a non-myeloablative preparatory regimen for allo HSCT. This will be determined by 100d Non-relapse mortality and 100d Graft rejection
Measured: 100 days post transplant
Secondary outcomes (1)
To obtain a preliminary estimate of the efficacy of this therapy as defined by: Complete remission at day 100 and One-year disease free survival.
Measured: 100 days and 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2003 (estimated)
- Study startNov 2002
- Primary completionMay 2005
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, George Carrum, Baylor College of Medicine
- Investigators
- Malcolm K Brenner, MD, Study chair, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00056966
- Sponsor's protocol ID
- 12472
- Other IDs
- ACHE
- Status last verified
- Jun 2012
- First submitted
- 26 Mar 2003
- Last updated
- 29 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of CD45 Antibodies and Alemtuzumab Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases
- ClinicalTrials.gov ID
- NCT00056966
- Acronym / sponsor ID
- 12472
- Conditions
- Hematologic Malignancy
- Keywords
- Acute myeloid leukemia, Acute lymphoblastic leukemia, Chronic myeloid leukemia, Non-Hodgkin's lymphoma, Hodgkin's disease, Myelodysplastic syndrome, Myeloproliferative disorders, Multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Nov 2002
- Primary completion
- May 2005 (actual)
- Study completion
- Dec 2006 (actual)
- First posted
- 27 Mar 2003 (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.
Participants in this study have a hematologic malignancy (a disorder in the bone marrow that affects the body's ability to create blood) that might benefit from receiving an allogeneic stem cell transplant (meaning the cells come from a donor) from a family member or nearly identical matched donor. The donor may either be a matched sibling, a mismatched family member, or an unrelated person.
Usually these patients are given high doses of chemotherapy before receiving a stem cell transplant to keep their immune system from rejecting the donor stem cells and to kill any diseased cells that remain in the body. However, this group of patients have a high risk of developing possibly life-threatening treatment-related side effects such as infections, damage to vital organs such as lungs, liver, kidney and heart, as well as graft versus host disease (GVHD).
Instead of the high dose chemotherapy and radiotherapy usually given before a transplant, this research study uses a new pre-transplant combination of three drugs, Fludarabine, Anti-CD45 and CAMPATH-1H with low dose radiotherapy. Fludarabine is a chemotherapy drug while Anti-CD45 and CAMPATH-1H are antibodies against certain types of blood cells, including those which are causing this disease. CAMPATH-1H is particularly important because it stays active in the body for a long time after it is given, which means it may work longer to prevent GVHD symptoms. Anti-CD45 may help in eradicating residual malignant cells. All these agents also help in preventing rejection of donor stem cells. This study is designed to give a less intense chemotherapy and radiotherapy, so that the life-threatening toxicities of conventional high dose chemotherapy and radiotherapy regimen can be reduced, while maintaining the ability to cure cancer.
Detailed description
CAMPATH-1H will be given as a daily IV infusion for three days. Fludarabine will be given as a daily IV infusion for four days. Anti-CD45 will be given as a daily IV infusion for 4 days. Patients will then receive radiotherapy (also known as Total Body Irradiation or TBI) for one day. A summary of the treatment follows:
- Day - 8: CAMPATH-1H and Fludarabine
- Day - 7: CAMPATH-1H and Fludarabine
- Day - 6: CAMPATH-1H and Fludarabine
- Day - 5: Anti-CD45 and Fludarabine
- Day - 4: Anti-CD45
- Day - 3: Anti-CD45
- Day - 2: Anti-CD45
- Day - 1: TBI
- Day 0: Stem Cell Infusion (transplant)
To help prevent the body from developing GVHD, patients will also receive the drug FK506, starting two days before the transplant and continuing for at least one month.
Both the CAMPATH-1H and the Anti-CD45 can cause allergic reactions so patients will be given drugs to help prevent those reactions before receiving daily doses.
To see how CAMPATH-1H works in patients with hematologic malignancies, some patients will be asked to participate in pharmacokinetic studies. For this, approximately 13 blood samples will be taken from the central line scheduled before each infusion on Day -8 to Day -6, daily thereafter until Day 0, and then approximately once per week on days 7, 14, 21 and 28 post transplant. No more than 5 teaspoonfuls total will be drawn.
To see how Anti-CD45 works in patients with hematologic malignancies some patients will be asked to participate in pharmacokinetic studies. Approximately 22 blood samples will be taken from the central line scheduled before, during and after each infusion and after the end of the last infusion of Anti-CD45. No more than 10 teaspoonfuls total will be drawn over the course of the four anti-CD45 infusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ANTI-CD45, Drug: CAMPATH-1H, Drug: FK506, Drug: Fludarabine, Radiation: Total Body Irradiation, Procedure: Stem cell infusionrecipients of HLA matched sibling transplants |
| 2 | Experimental | Drug: ANTI-CD45, Drug: CAMPATH-1H, Drug: FK506, Drug: Fludarabine, Radiation: Total Body Irradiation, Procedure: Stem cell infusionrecipients of unrelated or mismatched family donor transplants |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Patients with one of the following high risk diseases needing allogeneic hemopoietic stem cell transplantation:
- Acute myeloid leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
- Acute lymphoblastic leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
- Chronic myeloid leukemia, either a) Accelerated phase, or b) Blast crisis, or c) Chronic phase and not achieving major cytogenetic response despite standard therapy
- Chronic lymphocytic leukemia, either a) Primary refractory, or b) Beyond first complete remission(CR1),
Key exclusion criteria (7 listed)
- Pregnant and lactating women, or women unwilling to use contraception.
- HIV positive patient
- Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater)
- Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater)
- Child's class C cirrhosis
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 |
|---|---|---|
| ANTI-CD45400ug/kg Day-5 through Day-2 | Drug | 1, 2 |
| CAMPATH-1HAlso: anti-CD52, alemtuzumabDay -8 through Day -6 Dosed per Institutional SOP | Drug | 1, 2 |
| FK506Also: tacrolimusDay -2 through Day 30 dose adjusted to maintain level between 5-15 ng/ml. | Drug | 1, 2 |
| FludarabineDay-8 through Day-5 30 mg/m2 | Drug | 1, 2 |
| Total Body IrradiationDay-1 single dose 450 cGy | Radiation | 1, 2 |
| Stem cell infusionPatients will receive peripheral blood stem cells from a HLA matched or one antigen mismatched related or unrelated donor (target CD34+ cell count >2 x 106/kg). When peripheral stem cells are unavailable or insufficient, bone marrow (target mononuclear cell count >2 x 108/kg) will be substituted. | Procedure or surgery | 1, 2 |
Primary outcome
Assess safety and feasibility of monoclonal abs directed to CD45 and CD52 antigens, Fludarabine and low dose TBI, as a non-myeloablative preparatory regimen for allo HSCT. This will be determined by 100d Non-relapse mortality and 100d Graft rejection
Time frame: 100 days post transplant
1 secondary outcome
To obtain a preliminary estimate of the efficacy of this therapy as defined by: Complete remission at day 100 and One-year disease free survival.
Time frame: 100 days and 1 year post transplant
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 29 Jun 2012.
Related trials for Hematologic Malignancy
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
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.
Malcolm K Brenner, MD study chair
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ANTI-CD45, CAMPATH-1H and FK506 in people with Hematologic Malignancy, run by Baylor College of Medicine at 2 sites 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 24 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 29 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
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?
Assess safety and feasibility of monoclonal abs directed to CD45 and CD52 antigens, Fludarabine and low dose TBI, as a non-myeloablative preparatory regimen for allo HSCT. This will be determined by 100d Non-relapse mortality and 100d Graft rejection (time frame: 100 days post transplant). 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 29 Jun 2012.