Relapsed Acute LeukemiaPhase 1NCT01701375
A Phase 1 Trial of TST of PD 0332991 Followed by Cytarabine and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasia
A Phase 1 study testing PD 0332991 in people with Relapsed Acute Leukemia and Refractory Acute Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
1.1 Primary Objectives To determine the feasibility, tolerability, and toxicities of administering the selective CDK 4/6 inhibitor PD 0332991 prior to the combination of ara-C and Mitoxantrone for adults with relapsed and refractory acute leukemias and high risk myelodysplasias (MDS), including primary refractory… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Acute Leukemia, Refractory Acute Leukemia, High-Risk Myelodysplasia
- What is being tested?
- PD 0332991
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2012to Apr 2013
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults age ≥ 18 years
- Multilineage bone marrow failure
- Serum creatinine ≤ 2.0 mg/dl
- Hepatic enzymes (AST, ALT) ≤ 3x upper limit of normal (ULN)
- Bilirubin ≤ 2.0 mg/dl, unless due to Gilbert's disease, hemolysis or leukemic infiltration
- Left ventricular ejection fraction ≥ 45%
- QTc ≤ 470 msec
- RB expression is required for the action of PD 0332991. Because rb deletions and mutations are rare in acute leukemias and MDS, screening for RB expression will not be required before enrollment. Pretreatment biopsies will be stored and analyzed for RB expression if needed subsequently.
Who cannot join
- • No more than 5 cytotoxic regimens
- Previous allogeneic or autologous stem cell transplantation permitted
- ≥ 3 weeks delay from prior cytotoxic chemotherapy or radiation therapy
- ≥ 2 week delay from prior biologic therapies including hematopoietic growth factors and vidaza or decitabine
- If using Hydroxyurea, steroids, tyrosine kinase/src kinase inhibitors, arsenic, interferon for count control, must be off therapy for ≥ 48 hours prior to beginning PD 0332991
- No concomitant use of potent CYP450 3A4 inhibitors (e.g. triazole antifungal agents) or inducers (e.g. omperazole, dilantin, dexamethasone) within 7 days prior to beginning PD 0332991
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
Weill Cornell Medical Center
New York, New York, 10065
About this study
Official title: A Phase I and Pharmacodynamic Trial of Timed Sequential Administration of the Cyclin Dependent Kinase 4/6 Inhibitor PD 0332991 Followed by Cytarabine Plus Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasias
1.1 Primary Objectives
- To determine the feasibility, tolerability, and toxicities of administering the selective CDK 4/6 inhibitor PD 0332991 prior to the combination of ara-C and Mitoxantrone for adults with relapsed and refractory acute leukemias and high risk myelodysplasias (MDS), including primary refractory disease
- To determine the direct cytotoxic effects of single agent PD 0332991 on malignant blasts
- To determine the maximal tolerated dose (MTD) of PD 0332991 in timed sequential combination with ara-C and Mitoxantrone
- To determine if the timed sequential combination of PD 0332991 with ara-C and mitoxantrone can induce clinical responses in adults with relapsed or refractory acute leukemias and high-risk MDS
Read more
1.2 Secondary Objectives:
- To determine the ability of PD 0332991 to directly induce apoptosis in malignant cell populations in vivo
- To obtain pharmacodynamic (PD) data regarding the ability of PD 0332991 to arrest malignant cells in the G 1 phase of cell cycle, followed by synchronized release of those cells into S phase upon discontinuation of PD 0332991 and resultant enhanced ara-C cytotoxicity
- Being tested
- PD 0332991
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD 0332991Drug
- PD 0332991 will be given orally days 1,2,3
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | * PD 0332991 will be given orally days 1,2,3
* Cytarabine (ara-C) will be given by continuous 72 hour intravenous infusion beginning on day 6
* Mitoxantrone will be given over 2 hour infusion day 9, 12 hours after the completion of the ara-C infusion. The mitoxantrone dose may be reduced by 25-50% for patients who have received previous anthracyclines as determined by total previous anthracycline dose Receives: Drug: PD 0332991 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone.
The number of participants experiencing toxicities of administration of PD 0332991 in combination with cytarabine and mitoxantrone will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: 42 days
Secondary outcomes (1)
To Determine the Maximal Tolerated Dose (MTD) of PD 0332991 in Timed Sequential Combination With Ara-C and Mitoxantrone
Dose escalation decisions will be based on nonhematologic toxicities in Cycle 1 (28 days) and hematologic toxicities, in the case of an aplastic marrow through Day 56, For cytopenias including ANC < 500/mm3 or platelets < 50, 000/mm3 a bone marrow will be performed between days 42 and 49.. Dose limiting toxicity (DLT) will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2012 (estimated)
- Study startSep 2012
- Primary completionApr 2013
- Study completionApr 2013
Why it stopped: Material sponsor withdrew support
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 Relapsed Acute LeukemiaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society, Pfizer
- Responsible party
- Sponsor
- Investigators
- Judith Karp, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01701375
- Sponsor's protocol ID
- J1275
- Other IDs
- NA_00076003
- Status last verified
- Aug 2013
- First submitted
- 11 Sep 2012
- Last updated
- 9 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I and Pharmacodynamic Trial of Timed Sequential Administration of the Cyclin Dependent Kinase 4/6 Inhibitor PD 0332991 Followed by Cytarabine Plus Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasias
- ClinicalTrials.gov ID
- NCT01701375
- Acronym / sponsor ID
- J1275
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Material sponsor withdrew support
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society, Pfizer
- Study start
- Sep 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 5 Oct 2012 (estimated)
- Results
- Posted 9 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
1.1 Primary Objectives
- To determine the feasibility, tolerability, and toxicities of administering the selective CDK 4/6 inhibitor PD 0332991 prior to the combination of ara-C and Mitoxantrone for adults with relapsed and refractory acute leukemias and high risk myelodysplasias (MDS), including primary refractory disease
- To determine the direct cytotoxic effects of single agent PD 0332991 on malignant blasts
- To determine the maximal tolerated dose (MTD) of PD 0332991 in timed sequential combination with ara-C and Mitoxantrone
- To determine if the timed sequential combination of PD 0332991 with ara-C and mitoxantrone can induce clinical responses in adults with relapsed or refractory acute leukemias and high-risk MDS
1.2 Secondary Objectives:
- To determine the ability of PD 0332991 to directly induce apoptosis in malignant cell populations in vivo
- To obtain pharmacodynamic (PD) data regarding the ability of PD 0332991 to arrest malignant cells in the G 1 phase of cell cycle, followed by synchronized release of those cells into S phase upon discontinuation of PD 0332991 and resultant enhanced ara-C cytotoxicity
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: PD 0332991* PD 0332991 will be given orally days 1,2,3 * Cytarabine (ara-C) will be given by continuous 72 hour intravenous infusion beginning on day 6 * Mitoxantrone will be given over 2 hour infusion day 9, 12 hours after the completion of the ara-C infusion. The mitoxantrone dose may be reduced by 25-50% for patients who have received previous anthracyclines as determined by total previous anthracycline dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adults age ≥ 18 years
Key exclusion criteria (6 listed)
- • No more than 5 cytotoxic regimens
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 |
|---|---|---|
| PD 0332991• PD 0332991 will be given orally days 1,2,3 | Drug | Arm 1 |
Primary outcome
The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone.
Time frame: 42 days
The number of participants experiencing toxicities of administration of PD 0332991 in combination with cytarabine and mitoxantrone will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
1 secondary outcome
To Determine the Maximal Tolerated Dose (MTD) of PD 0332991 in Timed Sequential Combination With Ara-C and Mitoxantrone
Time frame: 42 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2013.
- 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.
Judith Karp, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PD 0332991 in people with Relapsed Acute Leukemia and Refractory Acute Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Sep 2013. 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 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?
Yes. Results are posted in the registry (first posted 9 Sep 2013). 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?
The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone. (time frame: 42 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 9 Sep 2013.