Chronic Myeloproliferative DisordersPhase 2NCT00053989
NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
A Phase 2 study testing anti-thymocyte globulin, graft-versus-tumor induction therapy and sargramostim in people with Chronic Myeloproliferative Disorders and Leukemia, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy 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. Read more about this study
- Who is it for?
- Ages 4 to 75 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- anti-thymocyte globulin, graft-versus-tumor induction therapy and sargramostim
- 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
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jan 2002to 19 Jul 2018
- Phase
- Phase 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 4 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of aplastic anemia
- Severe disease
- Failed at least 1 course of standard immunosuppressive regimen with cyclosporine and anti-thymocyte globulin OR
- Histologically confirmed hematologic malignancy including the following:
- Acute leukemia
- Any of the following types:
- Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes
- Secondary AML
- AML with high-risk cytogenetic abnormalities
- Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities
- Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen OR
- In first remission at high risk of relapse
- Chronic myelogenous leukemia
- Chronic phase meeting at least 1 of the following criteria:
- Failed imatinib mesylate
- Failed interferon after at least 6 months of treatment with minimum of 21 million units of interferon per week
- Unable to tolerate interferon
- Accelerated phase (blasts less than 20%)
- Myeloproliferative and myelodysplastic syndromes
- Myelofibrosis (after splenectomy)
- Refractory anemia
- Refractory anemia with excess blasts
- Chronic myelomonocytic leukemia
- Lymphoproliferative disease
- Chronic lymphocytic leukemia
- Symptomatic disease after first-line chemotherapy
- Low-grade non-Hodgkin's lymphoma (recurrent or persistent)
- Symptomatic disease after first-line chemotherapy
- Multiple myeloma
- Progressive disease after autologous stem cell transplantation
- Waldenstrom's macroglobulinemia
- Failed 1 standard regimen
- Non-Hodgkin's lymphoma meeting the following criteria:
- Intermediate or high grade
- Controlled and chemosensitive disease
- First remission lymphoblastic or small non-cleaved cell lymphoma at high risk of relapse
- Hodgkin's lymphoma
- Relapsed and chemosensitive disease
- Not eligible for standard myeloablative allogeneic stem cell transplantation
- Availability of any of the following donor types:
- Related donor matched at 5 or 6 HLA antigens (A, B, DR)
- Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci
- Single antigen mismatch at C allowed
- Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE: No syngeneic donors permitted
- No uncontrolled CNS disease (for hematologic malignancies) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age
- 4 to 75 (if related or unrelated donor peripheral blood or marrow transplantation)
- 4 to 60 (if unrelated cord blood transplantation)
Performance status
- Karnofsky > 50%
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- Bilirubin less than 3 times normal
- Alkaline phosphatase less than 3 times normal
- AST/ALT less than 3 times normal
- No Child's class B or C liver failure
Renal
- Creatinine clearance greater than 40 mL/min
Cardiovascular
- Cardiac ventricular ejection fraction at least 35% by MUGA
- No cardiovascular disease
Pulmonary
- DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV antibody negative
- No uncontrolled diabetes mellitus
- No active serious infection
- No other disease that would preclude study therapy
- No other concurrent malignancy except non-melanoma skin cancer
- No concurrent serious psychiatric illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- patients may have received a prior autologous blood or marrow transplantation (BMT)
- At least 6 months since prior allogeneic BMT
Chemotherapy
- See Disease Characteristics
- At least 2 weeks since prior chemotherapy, radiation or surgery
Endocrine therapy
- Not specified
Radiotherapy
- At least 2 weeks since prior radiotherapy
Surgery
- At least 2 weeks since prior surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
About this study
Official title: Non-Myeloablative Allogeneic Hematopoietic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Disorders
RATIONALE: Giving low doses of chemotherapy 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. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.
Read the detailed description
OBJECTIVES:
- Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.
- Determine clinical response and overall outcome of patients treated with this regimen.
- Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen.
OUTLINE:
- Preparative regimen:
- Matched related and unrelated donor transplantation:
- Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.
- Cord blood transplantation:
- Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.
- Graft-vs-host disease (GVHD) prophylaxis:
- Matched related and unrelated donor transplantation:
- Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.
- Cord blood transplantation:
- Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.
- Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
- Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.
Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Being tested
- anti-thymocyte globulin, graft-versus-tumor induction therapy, sargramostim, therapeutic allogeneic lymphocytes, cyclophosphamide
- Keywords
- accelerated phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, primary myelofibrosis, de novo myelodysplastic syndromes, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, refractory anemia with excess blasts, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, Waldenstrom macroglobulinemia, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult Hodgkin lymphoma, adult acute myeloid leukemia in remission, secondary acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
iv
graft-versus-tumor induction therapyBiological
iv
sargramostimBiological
iv
therapeutic allogeneic lymphocytesBiological
iv
cyclophosphamideDrug
injection
Also called FLUDARA
iv
oral
oral
tacrolimusDrug
oral
allogeneic bone marrow transplantationProcedure or surgery
iv
peripheral blood stem cell transplantationProcedure or surgery
iv
umbilical cord blood transplantationProcedure or surgery
iv
| Study group | Role | What they receive |
|---|---|---|
| All patients | Experimental | All patients enrolled on study Receives: Biological: anti-thymocyte globulin; Biological: graft-versus-tumor induction therapy; Biological: sargramostim; Biological: therapeutic allogeneic lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: allogeneic bone marrow transplantation; Procedure: peripheral blood stem cell transplantation; Procedure: umbilical cord blood transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Day 100 TRM
treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0
Measured: from start or conditioning (day -6 or -5) through day +100 after HSC infusion
Day 100 Best Response
Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol
Measured: from start of conditioning on day -6 or -5 through day +100 after HSC infusion
Secondary outcomes (3)
PFS
Progression free survival defined as time from HSC infusion (day 0) until progression of disease or death due to any cause. Patients are censored if alive without disease progression through 1 year after HSC infusion
Measured: 1 year
OS
Overall survival with events defined as death due to any cause and censored patients are alive as of 1 year post HSC infusion
Measured: 1 year
Acute GvHD
overall grade II-IV acute GvHD
Measured: Day +100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2003 (estimated)
- Study start29 Jan 2002
- Primary completion19 Jul 2018
- Study completion19 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philip L. McCarthy, MD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00053989
- Sponsor's protocol ID
- CDR0000269673
- Other IDs
- RP01-05
- Status last verified
- Dec 2019
- First submitted
- 5 Feb 2003
- Last updated
- 10 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Myeloablative Allogeneic Hematopoietic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Disorders
- ClinicalTrials.gov ID
- NCT00053989
- Acronym / sponsor ID
- CDR0000269673
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Keywords
- accelerated phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, primary myelofibrosis, de novo myelodysplastic syndromes, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, refractory anemia with excess blasts, stage I multiple myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Study start
- 29 Jan 2002 (actual)
- Primary completion
- 19 Jul 2018 (actual)
- Study completion
- 19 Jul 2018 (actual)
- First posted
- 6 Feb 2003 (estimated)
- Results
- Posted 10 Feb 2020
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 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. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.
Detailed description
OBJECTIVES:
- Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.
- Determine clinical response and overall outcome of patients treated with this regimen.
- Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen.
OUTLINE:
- Preparative regimen:
- Matched related and unrelated donor transplantation:
- Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.
- Cord blood transplantation:
- Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.
- Graft-vs-host disease (GVHD) prophylaxis:
- Matched related and unrelated donor transplantation:
- Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.
- Cord blood transplantation:
- Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.
- Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
- Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.
Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | Experimental | Biological: anti-thymocyte globulin, Biological: graft-versus-tumor induction therapy, Biological: sargramostim, Biological: therapeutic allogeneic lymphocytes, Drug: cyclophosphamide, Drug: fludarabine phosphate, Drug: methylprednisolone, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: allogeneic bone marrow transplantation, Procedure: peripheral blood stem cell transplantation, Procedure: umbilical cord blood transplantationAll patients enrolled on study |
Who may qualify
- Ages
- 4 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older 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 |
|---|---|---|
| anti-thymocyte globuliniv | Biological | All patients |
| graft-versus-tumor induction therapyiv | Biological | All patients |
| sargramostimiv | Biological | All patients |
| therapeutic allogeneic lymphocytesiv | Biological | All patients |
| cyclophosphamideinjection | Drug | All patients |
| fludarabine phosphateAlso: FLUDARAiv | Drug | All patients |
| methylprednisoloneoral | Drug | All patients |
| mycophenolate mofetiloral | Drug | All patients |
| tacrolimusoral | Drug | All patients |
| allogeneic bone marrow transplantationiv | Procedure or surgery | All patients |
| peripheral blood stem cell transplantationiv | Procedure or surgery | All patients |
| umbilical cord blood transplantationiv | Procedure or surgery | All patients |
Primary outcome
Day 100 TRM
Time frame: from start or conditioning (day -6 or -5) through day +100 after HSC infusion
treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0
Day 100 Best Response
Time frame: from start of conditioning on day -6 or -5 through day +100 after HSC infusion
Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol
3 secondary outcomes
PFS
Time frame: 1 year
OS
Time frame: 1 year
Acute GvHD
Time frame: Day +100
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Philip L. McCarthy, MD principal investigator
Roswell Park Cancer Institute
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 anti-thymocyte globulin, graft-versus-tumor induction therapy and sargramostim in people with Chronic Myeloproliferative Disorders and Leukemia, run by Roswell Park Cancer Institute 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?
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 10 Feb 2020. 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?
Yes. Results are posted in the registry (first posted 10 Feb 2020). 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?
Day 100 TRM (time frame: from start or conditioning (day -6 or -5) through day +100 after HSC infusion). 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?
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 10 Feb 2020.