LeukemiaPhase 1/2NCT00085449
Alemtuzumab Plus Fludarabine and Melphalan With or Without Cyclosporine, Mycophenolate Mofetil, and Low-Dose Total-Body Irradiation Therapy Followed by Donor Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer
A Phase 1/2 study testing alemtuzumab, cyclosporine and fludarabine phosphate in people with Leukemia and Lymphoma, run by Alliance for Clinical Trials in Oncology at 24 sites in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- alemtuzumab, cyclosporine and fludarabine phosphate
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 24 sitesUnited States
- Study dates
- May 2006to Jan 2007
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed hematological malignancy of 1 of the following types:
- Acute myeloid leukemia meeting at least 1 of the following criteria:
- Poor-risk cytogenetics, including -5, 5q-, -7, 7q-, 11q23, and Philadelphia (Ph) chromosome-positive in first or subsequent complete remission (CR)
- Relapsed or primary refractory disease with ≤ 10% blasts in the peripheral blood and ≤ 20% blasts in the bone marrow
- Standard-risk cytogenetics in second CR AND autologous transplantation is not feasible
- Standard-risk cytogenetics in third or subsequent CR
- Acute lymphoblastic leukemia meeting 1 of the following criteria:
- Second or subsequent CR
- High-risk cytogenetics, including Ph chromosome-positive and t(4:11) in first CR
- Relapsed or primarily refractory disease with ≤ 10% blasts in the peripheral blood and ≤ 20% blasts in the bone marrow
- High-risk myelodysplasia
- International Prognostic Scoring System Score ≥ 2.5
- Chronic myeloid leukemia (CML)* with an inadequate response to imatinib meeting 1 of the following criteria:
- Second or subsequent chronic phase
- Accelerated phase NOTE: *Patients with CML in blast crisis (> 30% promyelocytes and myeloblasts in the bone marrow) are not eligible
- Non-Hodgkin's lymphoma meeting 1 of the following criteria:
- Primarily refractory disease or in refractory relapse
- Relapsed disease after autologous stem cell transplantation
- Chemosensitive relapsed disease without CR to standard salvage therapy AND no option for autologous stem cell transplantation due to blood or marrow involvement or failure to harvest sufficient autologous stem cells
- Chronic lymphocytic leukemia meeting both of the following criteria:
- Stage III or IV disease
- Refractory to fludarabine
- Multiple myeloma meeting 1 of the following criteria:
- Primarily refractory disease or in refractory relapse
- Relapsed disease after autologous stem cell transplantation
- No relapsed disease < 6 months after autologous stem cell transplantation
- No available eligible HLA-matched (i.e., 5 of 6 or 6 of 6 antigen match for HLA-A, -B, and -DR loci) family donor by serological or molecular typing
- Available suitable family donor meeting the following criteria:
- Parent, sibling, or child of the recipient
- ≥ 16 years of age
- Identical for only one HLA haplotype (i.e., haploidentical) AND incompatible at the HLA-A, -B, -C, and -DR loci of the unshared haplotype by serological or molecular typing
- Mismatched with respect to KIR class I epitopes graft-vs-host directional activity
- Mismatching that predicts both graft-vs-host and host-vs-graft bi-directional activity eligible
- No mismatching that predicts only host-vs-graft directional activity
PATIENT CHARACTERISTICS:
Age
- 18 to 60
Performance status
- ECOG 0-1
Hepatic
- Bilirubin < 2 times upper limit of normal (ULN)
- AST and ALT < 2 times ULN
Renal
- Creatinine ≤ 2 mg/dL
Cardiovascular
- LVEF > 40% (corrected)
Pulmonary
- DLCO > 50% of predicted
Other
- No active infection requiring oral or IV antibiotics
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Concurrent corticosteroids allowed for adrenal failure, treatment of graft-vs-host disease, or as premedication during study
- No concurrent corticosteroids for antiemesis
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, 29425
University of Chicago Cancer Research Center
Chicago, Illinois, 60637-1470
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
Columbus, Ohio, 43210-1240
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, 52242-1009
Moores UCSD Cancer Center
La Jolla, California, 92093-0658
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
Los Angeles, California, 90048
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, 11030
University of Minnesota Cancer Center
Minneapolis, Minnesota, 55455
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Mount Sinai Medical Center
New York, New York, 10029
CCOP - Christiana Care Health Services
Newark, Delaware, 19713
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, 68198-7680
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, 07503
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298-0037
UCSF Comprehensive Cancer Center
San Francisco, California, 94115
Siteman Cancer Center at Barnes-Jewish Hospital
St Louis, Missouri, 63110
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1082
About this study
Official title: A Trial of Reduced Intensity Conditioning and Transplantation of Haplotype Mismatched and KIR Class I Epitope-Mismatched Highly Purified CD34 Cells
RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and total-body irradiation before donor peripheral blood stem cell transplant and to see how well they work in treating patients with relapsed or refractory hematologic cancer.
Read the detailed description
OBJECTIVES:
- Determine the ability of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and low-dose total body radiotherapy followed by haplotype-mismatched, KIR class I epitope-mismatched CD34-positive allogeneic peripheral blood stem cell transplantation to facilitate engraftment by day 35 post-transplantation in at least 85% of patients with relapsed, refractory, or poor-risk hematological malignancies.
- Determine the risk of graft-versus-host-disease in patients treated with these regimens.
- Determine, preliminarily, the efficacy of these regimens, in terms of progression-free survival, in these patients.
- Correlate outcomes, engraftment, and progression-free survival with the number of detectable alloreactive natural killer cell clones before transplantation and after engraftment in patients treated with these regimens.
- Determine immune reconstitution in patients treated with these regimens.
OUTLINE: This is a multicenter, pilot study. Patients are initially treated with conditioning regimen A. If adequate donor engraftment is not achieved, subsequent patients are treated with conditioning regimen B.
- Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2.
- Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1.
All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.
Patients are followed every 3 months for 1 year and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 14-56 patients (14-28 per regimen) will be accrued for this study.
- Conditions
- Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Being tested
- alemtuzumab, cyclosporine, fludarabine phosphate, melphalan, mycophenolate mofetil
- Keywords
- recurrent adult acute myeloid leukemia, adult acute myeloid leukemia in remission, recurrent adult acute lymphoblastic leukemia, adult acute lymphoblastic leukemia in remission, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic myelomonocytic leukemia, recurrent adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, recurrent mantle cell lymphoma, recurrent adult lymphoblastic lymphoma, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia
- Medical subject headings
- Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, 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.
alemtuzumabBiological
cyclosporineDrug
melphalanDrug
peripheral blood stem cell transplantationProcedure or surgery
radiation therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Regimen A + B | Experimental | Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2.
Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1.
All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.
Patients are followed every 3 months for 1 year and then every 6 months for 5 years. Receives: Biological: alemtuzumab; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: melphalan; Drug: mycophenolate mofetil; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment rate
Measured: Up to 6 years
Risk of graft-vs-host disease
Measured: Up to 6 years
Progression-free survival (PFS)
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2004 (estimated)
- Study startMay 2006
- Primary completionJan 2007
- Study completionJan 2007
Why it stopped: Funding cut, no patients enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sherif S. Farag, MD, PhD, Study chair, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00085449
- Sponsor's protocol ID
- CALGB-100102
- Other IDs
- CALGB-100102, CDR0000370797
- Status last verified
- Nov 2019
- First submitted
- 10 Jun 2004
- Last updated
- 27 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Reduced Intensity Conditioning and Transplantation of Haplotype Mismatched and KIR Class I Epitope-Mismatched Highly Purified CD34 Cells
- ClinicalTrials.gov ID
- NCT00085449
- Acronym / sponsor ID
- CALGB-100102
- Conditions
- Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Keywords
- recurrent adult acute myeloid leukemia, adult acute myeloid leukemia in remission, recurrent adult acute lymphoblastic leukemia, adult acute lymphoblastic leukemia in remission, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic myelomonocytic leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding cut, no patients enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2006
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jan 2007 (actual)
- First posted
- 11 Jun 2004 (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.
RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and total-body irradiation before donor peripheral blood stem cell transplant and to see how well they work in treating patients with relapsed or refractory hematologic cancer.
Detailed description
OBJECTIVES:
- Determine the ability of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and low-dose total body radiotherapy followed by haplotype-mismatched, KIR class I epitope-mismatched CD34-positive allogeneic peripheral blood stem cell transplantation to facilitate engraftment by day 35 post-transplantation in at least 85% of patients with relapsed, refractory, or poor-risk hematological malignancies.
- Determine the risk of graft-versus-host-disease in patients treated with these regimens.
- Determine, preliminarily, the efficacy of these regimens, in terms of progression-free survival, in these patients.
- Correlate outcomes, engraftment, and progression-free survival with the number of detectable alloreactive natural killer cell clones before transplantation and after engraftment in patients treated with these regimens.
- Determine immune reconstitution in patients treated with these regimens.
OUTLINE: This is a multicenter, pilot study. Patients are initially treated with conditioning regimen A. If adequate donor engraftment is not achieved, subsequent patients are treated with conditioning regimen B.
- Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2.
- Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1.
All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.
Patients are followed every 3 months for 1 year and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 14-56 patients (14-28 per regimen) will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regimen A + B | Experimental | Biological: alemtuzumab, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: melphalan, Drug: mycophenolate mofetil, Procedure: peripheral blood stem cell transplantation, Radiation: radiation therapyConditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2. Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1. All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients are followed every 3 months for 1 year and then every 6 months for 5 years. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
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 |
|---|---|---|
| alemtuzumab | Biological | Regimen A + B |
| cyclosporine | Drug | Regimen A + B |
| fludarabine phosphate | Drug | Regimen A + B |
| melphalan | Drug | Regimen A + B |
| mycophenolate mofetil | Drug | Regimen A + B |
| peripheral blood stem cell transplantation | Procedure or surgery | Regimen A + B |
| radiation therapy | Radiation | Regimen A + B |
Primary outcome
Engraftment rate
Time frame: Up to 6 years
Risk of graft-vs-host disease
Time frame: Up to 6 years
Progression-free survival (PFS)
Time frame: Up to 6 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2019.
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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.
Sherif S. Farag, MD, PhD study chair
Indiana University
24 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 alemtuzumab, cyclosporine and fludarabine phosphate in people with Leukemia and Lymphoma, run by Alliance for Clinical Trials in Oncology at 24 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?
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: withdrawn, as of the sponsor's last update on 27 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 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 was withdrawn before enrolling participants, so there are no results.
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?
Engraftment rate (time frame: Up to 6 years). The study lists 3 primary outcomes in all. 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 27 Nov 2019.